Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The IL-20 subfamily of cytokines — from host defence to tissue homeostasis

Key Points

  • Members of the interleukin-20 (IL-20) subfamily of cytokines are mainly produced by haematopoietic cells but these cytokines signal through receptors that are primarily expressed on epithelial tissues. These cytokines facilitate the communication between leukocytes and epithelial cells, and thereby enhance innate defence mechanisms and tissue repair processes at epithelial surfaces.

  • IL-20 subfamily cytokines stimulate the proliferation of epithelial cells and also their production of antimicrobial proteins, and pro-inflammatory cytokines and chemokines. All of these functions strengthen epithelial barrier function.

  • IL-22 is indispensable for host defence during infection with extracellular pathogens such as Citrobacter rodentium, Klebsiella pneumoniae and yeast. The roles of the other IL-20 subfamily cytokines during infection are still mostly undefined.

  • IL-20 subfamily cytokines are induced during wound healing in the skin and contribute to several stages of the wound-healing process, including inflammation, angiogenesis, re-epithelialization and remodelling.

  • IL-20 subfamily cytokines are not tumorigenic per se, but they can have both tumour-promoting and tumour-suppressive effects on tumours of epithelial origin, depending on the tumour stage and the local inflammatory environment.

  • Emerging data suggest that IL-22 — and presumably other IL-20 subfamily cytokines — can regulate metabolic processes such as lipid metabolism. IL-22 can also ameliorate metabolic syndrome by enhancing intestinal mucosal immunity and reducing chronic systemic inflammation.

Abstract

The interleukin-20 (IL-20) subfamily of cytokines comprises IL-19, IL-20, IL-22, IL-24 and IL-26. These cytokines are all members of the larger IL-10 family, but have been grouped together to form the IL-20 subfamily based on their usage of common receptor subunits and similarities in their target-cell profiles and biological functions. Members of the IL-20 subfamily facilitate the communication between leukocytes and epithelial cells, thereby enhancing innate defence mechanisms and tissue repair processes at epithelial surfaces. In this Review, we describe the cellular sources and targets of the IL-20 subfamily cytokines, and we detail how their expression is regulated. Much of our understanding of the unique biology of this group of cytokines is still based on IL-22, which is the most studied member of the IL-20 subfamily. Nevertheless, we attempt a broader discussion of the emerging functions of IL-20 subfamily cytokines in host defence, inflammatory diseases, cancer and metabolism.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The IL-20 subfamily of cytokines and their receptors.
Figure 2: IL-20 subfamily cytokines function in different stages during skin injury and promote topical wound healing.
Figure 3: IL-22 alleviates metabolic syndrome in multiple organs.

Similar content being viewed by others

References

  1. Ouyang, W., Rutz, S., Crellin, N. K., Valdez, P. A. & Hymowitz, S. G. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu. Rev. Immunol. 29, 71–109 (2011).

    CAS  PubMed  Google Scholar 

  2. Sabat, R., Ouyang, W. & Wolk, K. Therapeutic opportunities of the IL-22–IL-22R1 system. Nature Rev. Drug Discov. 13, 21–38 (2014).

    CAS  Google Scholar 

  3. Leng, R.-X., Pan, H.-F., Tao, J.-H. & Ye, D.-Q. IL-19, IL-20 and IL-24: potential therapeutic targets for autoimmune diseases. Expert Opin. Ther. Targets 15, 119–126 (2011).

    CAS  PubMed  Google Scholar 

  4. Gallagher, G. et al. Cloning, expression and initial characterization of interleukin-19 (IL-19), a novel homologue of human interleukin-10 (IL-10). Genes Immun. 1, 442–450 (2000).

    CAS  PubMed  Google Scholar 

  5. Blumberg, H. et al. Interleukin 20: discovery, receptor identification, and role in epidermal function. Cell 104, 9–19 (2001).

    CAS  PubMed  Google Scholar 

  6. Dumoutier, L., Louahed, J. & Renauld, J. C. Cloning and characterization of IL-10-related T cell-derived inducible factor (IL-TIF), a novel cytokine structurally related to IL-10 and inducible by IL-9. J. Immunol. 164, 1814–1819 (2000).

    CAS  PubMed  Google Scholar 

  7. Jiang, H., Lin, J. J., Su, Z. Z., Goldstein, N. I. & Fisher, P. B. Subtraction hybridization identifies a novel melanoma differentiation associated gene, mda-7, modulated during human melanoma differentiation, growth and progression. Oncogene 11, 2477–2486 (1995).

    CAS  PubMed  Google Scholar 

  8. Wang, T., Diaz-Rosales, P., Martin, S. A. & Secombes, C. J. Cloning of a novel interleukin (IL)-20-like gene in rainbow trout Oncorhynchus mykiss gives an insight into the evolution of the IL-10 family. Dev. Comp. Immunol. 34, 158–167 (2010).

    CAS  PubMed  Google Scholar 

  9. Knappe, A., Hor, S., Wittmann, S. & Fickenscher, H. Induction of a novel cellular homolog of interleukin-10, AK155, by transformation of T lymphocytes with herpesvirus saimiri. J. Virol. 74, 3881–3887 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Jones, E. A. & Flavell, R. A. Distal enhancer elements transcribe intergenic RNA in the IL-10 family gene cluster. J. Immunol. 175, 7437–7446 (2005).

    CAS  PubMed  Google Scholar 

  11. Pestka, S. et al. Interleukin-10 and related cytokines and receptors. Annu. Rev. Immunol. 22, 929–979 (2004).

    CAS  PubMed  Google Scholar 

  12. Aggarwal, S., Xie, M. H., Maruoka, M., Foster, J. & Gurney, A. L. Acinar cells of the pancreas are a target of interleukin-22. J. Interferon Cytokine Res. 21, 1047–1053 (2001).

    CAS  PubMed  Google Scholar 

  13. Kotenko, S. V. et al. Identification, cloning, and characterization of a novel soluble receptor that binds IL-22 and neutralizes its activity. J. Immunol. 166, 7096–7103 (2001).

    CAS  PubMed  Google Scholar 

  14. Xu, W. et al. A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist. Proc. Natl Acad. Sci. USA 98, 9511–9516 (2001).

    CAS  PubMed  Google Scholar 

  15. Martin, J. C. et al. Interleukin-22 binding protein (IL-22BP) is constitutively expressed by a subset of conventional dendritic cells and is strongly induced by retinoic acid. Mucosal Immunol. 7, 101–113 (2014).

    CAS  PubMed  Google Scholar 

  16. Huber, S. et al. IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine. Nature 491, 259–263 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Weathington, N. M. et al. Glycogen synthase kinase-3β stabilizes the interleukin (IL)-22 receptor from proteasomal degradation in murine lung epithelia. J. Biol. Chem. 289, 17610–17619 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Wolk, K., Kunz, S., Asadullah, K. & Sabat, R. Cutting edge: immune cells as sources and targets of the IL-10 family members? J. Immunol. 168, 5397–5402 (2002). References 5, 12 and 18 are the first studies to describe the expression of receptors for IL-20 subfamily cytokines on epithelial tissues, which defined this group of cytokines as a means of communication between the immune system and the epithelium.

    CAS  PubMed  Google Scholar 

  19. Zheng, Y. et al. Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 445, 648–651 (2007).

    CAS  PubMed  Google Scholar 

  20. Zheng, Y. et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nature Med. 14, 282–289 (2008).

    CAS  PubMed  Google Scholar 

  21. de Luca, A. et al. IL-22 defines a novel immune pathway of antifungal resistance. Mucosal Immunol. 3, 361–373 (2010).

    CAS  PubMed  Google Scholar 

  22. Pickert, G. et al. STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing. J. Exp. Med. 206, 1465–1472 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Zindl, C. L. et al. IL-22-producing neutrophils contribute to antimicrobial defense and restitution of colonic epithelial integrity during colitis. Proc. Natl Acad. Sci. USA 110, 12768–12773 (2013).

    CAS  PubMed  Google Scholar 

  24. Wang, F. et al. Prominent production of IL-20 by CD68+/CD11c+ myeloid-derived cells in psoriasis: Gene regulation and cellular effects. J. Investigative Dermatol. 126, 1590–1599 (2006).

    CAS  Google Scholar 

  25. Wolk, K. et al. Maturing dendritic cells are an important source of IL-29 and IL-20 that may cooperatively increase the innate immunity of keratinocytes. J. Leukoc. Biol. 83, 1181–1193 (2008).

    CAS  PubMed  Google Scholar 

  26. Sa, S. M. et al. The effects of IL-20 subfamily cytokines on reconstituted human epidermis suggest potential roles in cutaneous innate defense and pathogenic adaptive immunity in psoriasis. J. Immunol. 178, 2229–2240 (2007). This is the first study to define IL-20 subfamily cytokines on the basis of receptor expression and to carry out a comparative analysis of downstream functions in the skin.

    CAS  PubMed  Google Scholar 

  27. Yano, S., Banno, T., Walsh, R. & Blumenberg, M. Transcriptional responses of human epidermal keratinocytes to cytokine interleukin-1. J. Cell. Physiol. 214, 1–13 (2008).

    CAS  PubMed  Google Scholar 

  28. Hunt, D. W. et al. Ultraviolet B light stimulates interleukin-20 expression by human epithelial keratinocytes. Photochem. Photobiol. 82, 1292–1300 (2006).

    CAS  PubMed  Google Scholar 

  29. Wolk, K. et al. The Th17 cytokine IL-22 induces IL-20 production in keratinocytes: a novel immunological cascade with potential relevance in psoriasis. Eur. J. Immunol. 39, 3570–3581 (2009).

    CAS  PubMed  Google Scholar 

  30. Aujla, S. J. et al. IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nature Med. 14, 275–281 (2008).

    CAS  PubMed  Google Scholar 

  31. Huang, F. et al. Potentiation of IL-19 expression in airway epithelia by IL-17A and IL-4/IL-13: important implications in asthma. J. Allergy Clin. Immunol. 121, 1415–1421 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Rutz, S., Eidenschenk, C. & Ouyang, W. IL-22, not simply a Th17 cytokine. Immunol. Rev. 252, 116–132 (2013).

    PubMed  Google Scholar 

  33. Ouyang, W., Kolls, J. K. & Zheng, Y. The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 28, 454–467 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Colonna, M. Interleukin-22-producing natural killer cells and lymphoid tissue inducer-like cells in mucosal immunity. Immunity 31, 15–23 (2009).

    CAS  PubMed  Google Scholar 

  35. Cupedo, T. et al. Human fetal lymphoid tissue-inducer cells are interleukin 17-producing precursors to RORC+ CD127+ natural killer-like cells. Nature Immunol. 10, 66–74 (2009).

    CAS  Google Scholar 

  36. Martin, B., Hirota, K., Cua, D. J., Stockinger, B. & Veldhoen, M. Interleukin-17-producing γδ T cells selectively expand in response to pathogen products and environmental signals. Immunity 31, 321–330 (2009).

    CAS  PubMed  Google Scholar 

  37. Sutton, C. E. et al. Interleukin-1 and IL-23 induce innate IL-17 production from γδ T cells, amplifying Th17 responses and autoimmunity. Immunity 31, 331–341 (2009).

    CAS  PubMed  Google Scholar 

  38. Takatori, H. et al. Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22. J. Exp. Med. 206, 35–41 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Spits, H. et al. Innate lymphoid cells — a proposal for uniform nomenclature. Nature Rev. Immunology 13, 145–149 (2013).

    CAS  Google Scholar 

  40. Satoh-Takayama, N. et al. Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity 29, 958–970 (2008).

    CAS  PubMed  Google Scholar 

  41. Luci, C. et al. Influence of the transcription factor RORγt on the development of NKp46+ cell populations in gut and skin. Nature Immunol. 10, 75–82 (2009).

    CAS  Google Scholar 

  42. Sanos, S. L. et al. RORγt and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells. Nature Immunol. 10, 83–91 (2009).

    CAS  Google Scholar 

  43. Cella, M. et al. A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature 457, 722–725 (2009).

    CAS  PubMed  Google Scholar 

  44. Crellin, N. K., Trifari, S., Kaplan, C. D., Cupedo, T. & Spits, H. Human NKp44+IL-22+ cells and LTi-like cells constitute a stable RORC+ lineage distinct from conventional natural killer cells. J. Exp. Med. 207, 281–290 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Liang, S. C. et al. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J. Exp. Med. 203, 2271–2279 (2006). References 19 and 45 identify IL-22 as a T H 17 cell cytokine and pioneer research into IL-22 biology.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Chung, Y. et al. Expression and regulation of IL-22 in the IL-17-producing CD4+ T lymphocytes. Cell Res. 16, 902–907 (2006).

    CAS  PubMed  Google Scholar 

  47. Gurney, A. L. IL-22, a Th1 cytokine that targets the pancreas and select other peripheral tissues. Int. Immunopharmacol. 4, 669–677 (2004).

    CAS  PubMed  Google Scholar 

  48. Duhen, T., Geiger, R., Jarrossay, D., Lanzavecchia, A. & Sallusto, F. Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells. Nature Immunol. 10, 857–863 (2009).

    CAS  Google Scholar 

  49. Eyerich, S. et al. Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. J. Clin. Invest. 119, 3573–3585 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Trifari, S., Kaplan, C. D., Tran, E. H., Crellin, N. K. & Spits, H. Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from TH-17, TH1 and TH2 cells. Nature Immunol. 10, 864–871 (2009).

    CAS  Google Scholar 

  51. Basu, R. et al. Th22 cells are an important source of IL-22 for host protection against enteropathogenic bacteria. Immunity 37, 1061–1075 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. McGeachy, M. J. et al. TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell-mediated pathology. Nature Immunol. 8, 1390–1397 (2007).

    CAS  Google Scholar 

  53. Nurieva, R. et al. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448, 480–483 (2007).

    CAS  PubMed  Google Scholar 

  54. Kreymborg, K. et al. IL-22 is expressed by Th17 cells in an IL-23-dependent fashion, but not required for the development of autoimmune encephalomyelitis. J. Immunol. 179, 8098–8104 (2007).

    CAS  PubMed  Google Scholar 

  55. Siegemund, S. et al. Differential IL-23 requirement for IL-22 and IL-17A production during innate immunity against Salmonella enterica serovar Enteritidis. Int. Immunol. 21, 555–565 (2009).

    CAS  PubMed  Google Scholar 

  56. Mus, A. M. C. et al. Interleukin-23 promotes Th17 differentiation by inhibiting T-bet and FoxP3 and is required for elevation of interleukin-22, but not interleukin-21, in autoimmune experimental arthritis. Arthritis Rheum. 62, 1043–1050 (2010).

    CAS  PubMed  Google Scholar 

  57. Mukherjee, S., Schaller, M. A., Neupane, R., Kunkel, S. L. & Lukacs, N. W. Regulation of T cell activation by Notch ligand, DLL4, promotes IL-17 production and Rorc activation. J. Immunol. 182, 7381–7388 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Alam, M. S. et al. Notch signaling drives IL-22 secretion in CD4+ T cells by stimulating the aryl hydrocarbon receptor. Proc. Natl Acad. Sci. USA 107, 5943–5948 (2010).

    PubMed  Google Scholar 

  59. Veldhoen, M., Hirota, K., Christensen, J., O'Garra, A. & Stockinger, B. Natural agonists for aryl hydrocarbon receptor in culture medium are essential for optimal differentiation of Th17 T cells. J. Exp. Med. 206, 43–49 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Veldhoen, M. et al. The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 453, 106–109 (2008).

    CAS  PubMed  Google Scholar 

  61. Schaefer, G., Venkataraman, C. & Schindler, U. Cutting edge: FISP (IL-4-induced secreted protein), a novel cytokine-like molecule secreted by Th2 cells. J. Immunol. 166, 5859–5863 (2001).

    CAS  PubMed  Google Scholar 

  62. Stevens, L. et al. Involvement of GATA3 in protein kinase C θ-induced Th2 cytokine expression. Eur. J. Immunol. 36, 3305–3314 (2006).

    CAS  PubMed  Google Scholar 

  63. Sahoo, A. et al. Stat6 and c-Jun mediate Th2 cell-specific IL-24 gene expression. J. Immunol. 186, 4098–4109 (2011).

    CAS  PubMed  Google Scholar 

  64. Wilson, N. J. et al. Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nature Immunol. 8, 950–957 (2007).

    CAS  Google Scholar 

  65. Manel, N., Unutmaz, D. & Littman, D. R. The differentiation of human TH-17 cells requires transforming growth factor-β and induction of the nuclear receptor RORγt. Nature Immunol. 9, 641–649 (2008).

    CAS  Google Scholar 

  66. Crellin, N. K. et al. Regulation of cytokine secretion in human CD127+ LTi-like innate lymphoid cells by Toll-like receptor 2. Immunity 33, 752–764 (2010).

    CAS  PubMed  Google Scholar 

  67. Satpathy, A. T. et al. Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens. Nature Immunol. 14, 937–948 (2013).

    CAS  Google Scholar 

  68. Van Maele, L. et al. TLR5 signaling stimulates the innate production of IL-17 and IL-22 by CD3negCD127+ immune cells in spleen and mucosa. J. Immunol. 185, 1177–1185 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Bogunovic, M. et al. Origin of the lamina propria dendritic cell network. Immunity 31, 513–525 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Varol, C. et al. Intestinal lamina propria dendritic cell subsets have different origin and functions. Immunity 31, 502–512 (2009).

    CAS  PubMed  Google Scholar 

  71. Coombes, J. L. & Maloy, K. J. Control of intestinal homeostasis by regulatory T cells and dendritic cells. Semin. Immunol. 19, 116–126 (2007).

    CAS  PubMed  Google Scholar 

  72. Kinnebrew, M. A. et al. Interleukin 23 production by intestinal CD103+CD11b+ dendritic cells in response to bacterial flagellin enhances mucosal innate immune defense. Immunity 36, 276–287 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Kinnebrew, M. A. et al. Bacterial flagellin stimulates Toll-like receptor 5–dependent defense against vancomycin-resistant Enterococcus infection. J. Infect. Dis. 201, 534–543 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Ota, N. et al. IL-22 bridges the lymphotoxin pathway with the maintenance of colonic lymphoid structures during infection with Citrobacter rodentium. Nature Immunol. 12, 941–948 (2011).

    CAS  Google Scholar 

  75. Tumanov, A. V. et al. Lymphotoxin controls the IL-22 protection pathway in gut innate lymphoid cells during mucosal pathogen challenge. Cell Host Microbe 10, 44–53 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Spahn, T. W. et al. The lymphotoxin-β receptor is critical for control of murine Citrobacter rodentium-induced colitis. Gastroenterology 127, 1463–1473 (2004).

    CAS  PubMed  Google Scholar 

  77. Wang, Y. et al. Lymphotoxin β receptor signaling in intestinal epithelial cells orchestrates innate immune responses against mucosal bacterial infection. Immunity 32, 403–413 (2010).

    PubMed  PubMed Central  Google Scholar 

  78. Manta, C. et al. CX3CR1+ macrophages support IL-22 production by innate lymphoid cells during infection with Citrobacter rodentium. Mucosal Immunol. 6, 177–188 (2013). References 67, 72 and 78 investigate the upstream cell types required for induction of IL-22 during infection.

    CAS  PubMed  Google Scholar 

  79. Sonnenberg, G. F., Monticelli, L. A., Elloso, M. M., Fouser, L. A. & Artis, D. CD4+ lymphoid tissue-inducer cells promote innate immunity in the gut. Immunity 34, 122–134 (2011).

    CAS  PubMed  Google Scholar 

  80. Zigmond, E. et al. Ly6Chi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells. Immunity 37, 1076–1090 (2012).

    CAS  PubMed  Google Scholar 

  81. Kim, Y.-G. et al. The Nod2 sensor promotes intestinal pathogen eradication via the chemokine CCL2-dependent recruitment of inflammatory monocytes. Immunity 34, 769–780 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Colonna, M. Skin function for human CD1a-reactive T cells. Nature Immunol. 11, 1079–1080 (2010).

    CAS  Google Scholar 

  83. de Jong, A. et al. CD1a-autoreactive T cells are a normal component of the human αβ T cell repertoire. Nature Immunol. 11, 1102–1109 (2010).

    CAS  Google Scholar 

  84. Sonnenberg, G. F., Fouser, L. A. & Artis, D. Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22. Nature Immunol. 12, 383–390 (2011).

    CAS  Google Scholar 

  85. Hackstein, H. et al. Modulation of respiratory dendritic cells during Klebsiella pneumonia infection. Respir. Res. 14, 91 (2013).

    PubMed  PubMed Central  Google Scholar 

  86. Ermers, M. J. et al. IL10 family member genes IL19 and IL20 are associated with recurrent wheeze after respiratory syncytial virus bronchiolitis. Pediatr. Res. 70, 518–523 (2011).

    CAS  PubMed  Google Scholar 

  87. Sonnenberg, G. F. et al. Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria. Science 336, 1321–1325 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Eidenschenk, C., Rutz, S., Liesenfeld, O. & Ouyang, W. Role of IL-22 in microbial host defense. Curr. Top. Microbiol. Immunol. 380, 213–236 (2014).

    CAS  PubMed  Google Scholar 

  89. Paget, C. et al. Interleukin-22 is produced by invariant natural killer T lymphocytes during influenza A virus infection: potential role in protection against lung epithelial damages. J. Biol. Chem. 287, 8816–8829 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Wolk, K. et al. IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur. J. Immunol. 36, 1309–1323 (2006).

    CAS  PubMed  Google Scholar 

  91. Boniface, K. et al. IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes. J. Immunol. 174, 3695–3702 (2005).

    CAS  PubMed  Google Scholar 

  92. Dambacher, J. et al. The role of the novel Th17 cytokine IL-26 in intestinal inflammation. Gut 58, 1207–1217 (2009).

    CAS  PubMed  Google Scholar 

  93. Behnsen, J. et al. The cytokine IL-22 promotes pathogen colonization by suppressing related commensal bacteria. Immunity 40, 262–273 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Liu, J. Z. et al. Zinc sequestration by the neutrophil protein calprotectin enhances Salmonella growth in the inflamed gut. Cell Host Microbe 11, 227–239 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Raffatellu, M. et al. Lipocalin-2 resistance confers an advantage to Salmonella enterica serotype Typhimurium for growth and survival in the inflamed intestine. Cell Host Microbe 5, 476–486 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Stelter, C. et al. Salmonella-induced mucosal lectin RegIIIβ kills competing gut microbiota. PLoS ONE 6, e20749 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Winter, S. E., Lopez, C. A. & Baumler, A. J. The dynamics of gut-associated microbial communities during inflammation. EMBO Rep. 14, 319–327 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Myles, I. A. et al. Signaling via the IL-20 receptor inhibits cutaneous production of IL-1β and IL-17A to promote infection with methicillin-resistant Staphylococcus aureus. Nature Immunol. 14, 804–811 (2013). This study reports a specific function for IL-19, IL-20 and IL-24 during infection.

    CAS  Google Scholar 

  99. Miller, L. S. et al. MyD88 mediates neutrophil recruitment initiated by IL-1R but not TLR2 activation in immunity against Staphylococcus aureus. Immunity 24, 79–91 (2006).

    CAS  PubMed  Google Scholar 

  100. Cho, J. S. et al. IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice. J. Clin. Invest. 120, 1762–1773 (2010).

    PubMed  PubMed Central  Google Scholar 

  101. Lowes, M. A., Bowcock, A. M. & Krueger, J. G. Pathogenesis and therapy of psoriasis. Nature 445, 866–873 (2007).

    CAS  PubMed  Google Scholar 

  102. He, M. & Liang, P. IL-24 transgenic mice: in vivo evidence of overlapping functions for IL-20, IL-22, and IL-24 in the epidermis. J. Immunol. 184, 1793–1798 (2010).

    CAS  PubMed  Google Scholar 

  103. Wolk, K. et al. IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-γ are not. J. Mol. Med. 87, 523–536 (2009).

    CAS  PubMed  Google Scholar 

  104. Wolk, K. et al. IL-22 increases the innate immunity of tissues. Immunity 21, 241–254 (2004). References 91 and 104 provide the first description of the downstream functions of IL-22 and define the biology of IL-20 subfamily cytokines.

    CAS  PubMed  Google Scholar 

  105. Romer, J. et al. Epidermal overexpression of interleukin-19 and -20 mRNA in psoriatic skin disappears after short-term treatment with cyclosporine a or calcipotriol. J. Invest. Dermatol. 121, 1306–1311 (2003).

    CAS  PubMed  Google Scholar 

  106. Otkjaer, K. et al. The dynamics of gene expression of interleukin-19 and interleukin-20 and their receptors in psoriasis. Br. J. Dermatol. 153, 911–918 (2005).

    CAS  PubMed  Google Scholar 

  107. Ouyang, W. Distinct roles of IL-22 in human psoriasis and inflammatory bowel disease. Cytokine Growth Factor Rev. 21, 435–441 (2010).

    CAS  PubMed  Google Scholar 

  108. Brand, S. et al. IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and intestinal epithelial cell migration. Am. J. Physiol. Gastrointest. Liver Physiol. 290, G827–G838 (2006).

    CAS  PubMed  Google Scholar 

  109. Andoh, A. et al. Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts. Gastroenterology 129, 969–984 (2005).

    CAS  PubMed  Google Scholar 

  110. Sugimoto, K. et al. IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. J. Clin. Invest. 118, 534–544 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Zenewicz, L. A. et al. Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity 29, 947–957 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Neufert, C. et al. Activation of epithelial STAT3 regulates intestinal homeostasis. Cell Cycle 9, 652–655 (2010).

    CAS  PubMed  Google Scholar 

  113. Fonseca-Camarillo, G., Furuzawa-Carballeda, J., Granados, J. & Yamamoto-Furusho, J. K. Expression of interleukin (IL)-19 and IL-24 in inflammatory bowel disease patients: a cross-sectional study. Clin. Exp. Immunol. 177, 64–75 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Fonseca-Camarillo, G., Furuzawa-Carballeda, J., Llorente, L. & Yamamoto-Furusho, J. K. IL-10- and IL-20-expressing epithelial and inflammatory cells are increased in patients with ulcerative colitis. J. Clin. Immunol. 33, 640–648 (2013).

    CAS  PubMed  Google Scholar 

  115. Andoh, A. et al. Expression of IL-24, an activator of the JAK1/STAT3/SOCS3 cascade, is enhanced in inflammatory bowel disease. J. Immunol. 183, 687–695 (2009).

    CAS  PubMed  Google Scholar 

  116. Azuma, Y. T. et al. Interleukin-19 protects mice from innate-mediated colonic inflammation. Inflamm. Bowel Dis. 16, 1017–1028 (2010).

    PubMed  Google Scholar 

  117. Sakurai, N. et al. Expression of IL-19 and its receptors in RA: potential role for synovial hyperplasia formation. Rheumatol. 47, 815–820 (2008).

    CAS  Google Scholar 

  118. Ikeuchi, H. et al. Expression of interleukin-22 in rheumatoid arthritis: potential role as a proinflammatory cytokine. Arthritis Rheum. 52, 1037–1046 (2005).

    CAS  PubMed  Google Scholar 

  119. Kragstrup, T. W. et al. The expression of IL-20 and IL-24 and their shared receptors are increased in rheumatoid arthritis and spondyloarthropathy. Cytokine 41, 16–23 (2008).

    CAS  PubMed  Google Scholar 

  120. Corvaisier, M. et al. IL-26 is overexpressed in rheumatoid arthritis and induces proinflammatory cytokine production and Th17 cell generation. PLoS Biol. 10, e1001395 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Alanara, T., Karstila, K., Moilanen, T., Silvennoinen, O. & Isomaki, P. Expression of IL-10 family cytokines in rheumatoid arthritis: elevated levels of IL-19 in the joints. Scand. J. Rheumatol 39, 118–126 (2010).

    CAS  PubMed  Google Scholar 

  122. Hsu, Y.-H. et al. Function of interleukin-20 as a proinflammatory molecule in rheumatoid and experimental arthritis. Arthritis Rheum. 54, 2722–2733 (2006).

    CAS  PubMed  Google Scholar 

  123. Pène, J. et al. Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes. J. Immunol. 180, 7423–7430 (2008).

    PubMed  Google Scholar 

  124. Shen, H., Goodall, J. C. & Hill Gaston, J. S. Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis Rheum. 60, 1647–1656 (2009).

    CAS  PubMed  Google Scholar 

  125. Leipe, J. et al. Interleukin 22 serum levels are associated with radiographic progression in rheumatoid arthritis. Ann. Rheum. Dis. 70, 1453–1457 (2011).

    CAS  PubMed  Google Scholar 

  126. Zhang, L. et al. Increased frequencies of Th22 cells as well as Th17 cells in the peripheral blood of patients with ankylosing spondylitis and rheumatoid arthritis. PLoS ONE 7, e31000 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Hsu, Y. H., Hsieh, P. P. & Chang, M. S. Interleukin-19 blockade attenuates collagen-induced arthritis in rats. Rheumatol. 51, 434–442 (2012).

    CAS  Google Scholar 

  128. Zhang, L. et al. Elevated Th22 cells correlated with Th17 cells in patients with rheumatoid arthritis. J. Clin. Immunol. 31, 606–614 (2011).

    CAS  PubMed  Google Scholar 

  129. da Rocha, L. F. et al. Increased serum interleukin 22 in patients with rheumatoid arthritis and correlation with disease activity. J. Rheumatol. 39, 1320–1325 (2012).

    PubMed  Google Scholar 

  130. Geboes, L. et al. Proinflammatory role of the Th17 cytokine interleukin-22 in collagen-induced arthritis in C57BL/6 mice. Arthritis Rheum. 60, 390–395 (2009).

    CAS  PubMed  Google Scholar 

  131. Justa, S., Zhou, X. & Sarkar, S. Endogenous IL-22 plays a dual role in arthritis: regulation of established arthritis via IFN-γ responses. PLoS ONE 9, e93279 (2014).

    PubMed  PubMed Central  Google Scholar 

  132. Marijnissen, R. J. et al. Increased expression of interleukin-22 by synovial Th17 cells during late stages of murine experimental arthritis is controlled by interleukin-1 and enhances bone degradation. Arthritis Rheum. 63, 2939–2948 (2011).

    CAS  PubMed  Google Scholar 

  133. Sherlock, J. P. et al. IL-23 induces spondyloarthropathy by acting on ROR-γt+ CD3+CD4CD8 entheseal resident T cells. Nature Med. 18, 1069–1076 (2012).

    CAS  PubMed  Google Scholar 

  134. Benham, H. et al. IL-23-mediates the intestinal response to microbial β-glucan and the development of spondyloarthritis pathology in SKG mice. Arthritis Rheumatol. 66, 1755–1767 (2014).

    CAS  PubMed  Google Scholar 

  135. Benham, H. et al. Th17 and Th22 cells in psoriatic arthritis and psoriasis. Arthritis Res. Ther. 15, R136 (2013).

    PubMed  PubMed Central  Google Scholar 

  136. Ortonne, J. P. Aetiology and pathogenesis of psoriasis. Br. J. Dermatol. 135 (Suppl. 49), 1–5 (1996).

    PubMed  Google Scholar 

  137. Sano, S. et al. Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Nature Med. 11, 43–49 (2005).

    CAS  PubMed  Google Scholar 

  138. Sun, D. P. et al. Interleukin (IL)-19 promoted skin wound healing by increasing fibroblast keratinocyte growth factor expression. Cytokine 62, 360–368 (2013).

    CAS  PubMed  Google Scholar 

  139. McGee, H. M. et al. IL-22 promotes fibroblast-mediated wound repair in the skin. J. Invest. Dermatol. 133, 1321–1329 (2013). References 138 and 139 define the functions of IL-20 subfamily cytokines in wound healing.

    CAS  PubMed  Google Scholar 

  140. Poindexter, N. J. et al. IL-24 is expressed during wound repair and inhibits TGFα-induced migration and proliferation of keratinocytes. Exp. Dermatol. 19, 714–722 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  141. Bao, P. et al. The role of vascular endothelial growth factor in wound healing. J. Surg. Res. 153, 347–358 (2009).

    CAS  PubMed  Google Scholar 

  142. Perera, G. K. et al. Integrative biology approach identifies cytokine targeting strategies for psoriasis. Sci. Transl. Med. 6, 223ra22 (2014).

    PubMed  Google Scholar 

  143. Hanash, A. M. et al. Interleukin-22 protects intestinal stem cells from immune-mediated tissue damage and regulates sensitivity to graft versus host disease. Immunity 37, 339–350 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Radaeva, S., Sun, R., Pan, H. N., Hong, F. & Gao, B. Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation. Hepatology 39, 1332–1342 (2004).

    CAS  PubMed  Google Scholar 

  145. Zenewicz, L. A. et al. Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation. Immunity 27, 647–659 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Pan, H., Hong, F., Radaeva, S. & Gao, B. Hydrodynamic gene delivery of interleukin-22 protects the mouse liver from concanavalin A-, carbon tetrachloride-, and Fas ligand-induced injury via activation of STAT3. Cell. Mol. Immunol. 1, 43–49 (2004).

    CAS  PubMed  Google Scholar 

  147. Park, O. et al. In vivo consequences of liver-specific interleukin-22 expression in mice: implications for human liver disease progression. Hepatology 54, 252–261 (2011).

    PubMed  PubMed Central  Google Scholar 

  148. Ki, S. H. et al. Interleukin-22 treatment ameliorates alcoholic liver injury in a murine model of chronic-binge ethanol feeding: role of signal transducer and activator of transcription 3. Hepatology 52, 1291–1300 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Kong, X. et al. Interleukin-22 induces hepatic stellate cell senescence and restricts liver fibrosis in mice. Hepatology 56, 1150–1159 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Ren, X. & Colletti, L. M. IL-22 is involved in liver regeneration after hepatectomy. Am. J. Physiol. Gastrointest Liver Physiol. 298, G74–G80 (2009).

    PubMed  PubMed Central  Google Scholar 

  151. Xue, J., Nguyen, D. T. & Habtezion, A. Aryl hydrocarbon receptor regulates pancreatic IL-22 production and protects mice from acute pancreatitis. Gastroenterology 143, 1670–1680 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Feng, D. et al. Interleukin-22 ameliorates cerulein-induced pancreatitis in mice by inhibiting the autophagic pathway. Int. J. Biol. Sci. 8, 249–257 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Kulkarni, O. P. et al. Toll-like receptor 4-induced IL-22 accelerates kidney regeneration. J. Am. Soc. Nephrol. 25, 978–989 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Xu, M. J. et al. IL-22 ameliorates renal ischemia-reperfusion injury by targeting proximal tubule epithelium. J. Am. Soc. Nephrol. 25, 967–977 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Dudakov, J. A. et al. Interleukin-22 drives endogenous thymic regeneration in mice. Science 336, 91–95 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Hsu, Y. H. et al. Interleukin-19 mediates tissue damage in murine ischemic acute kidney injury. PLoS ONE 8, e56028 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Chiu, Y. S., Wei, C. C., Lin, Y. J., Hsu, Y. H. & Chang, M. S. IL-20 and IL-20R1 antibodies protect against liver fibrosis. Hepatology 60, 1003–1014 (2014).

    CAS  PubMed  Google Scholar 

  158. Hsu, Y. H. et al. Anti-IL-20 monoclonal antibody suppresses breast cancer progression and bone osteolysis in murine models. J. Immunol. 188, 1981–1991 (2012).

    CAS  PubMed  Google Scholar 

  159. Baird, A. M., Gray, S. G. & O'Byrne, K. J. IL-20 is epigenetically regulated in NSCLC and down regulates the expression of VEGF. Eur. J. Cancer 47, 1908–1918 (2011).

    CAS  PubMed  Google Scholar 

  160. Hsu, Y. H., Wei, C. C., Shieh, D. B., Chan, C. H. & Chang, M. S. Anti-IL-20 monoclonal antibody alleviates inflammation in oral cancer and suppresses tumor growth. Mol. Cancer Res. 10, 1430–1439 (2012).

    CAS  PubMed  Google Scholar 

  161. Lee, S. J. et al. Interleukin-20 promotes migration of bladder cancer cells through extracellular signal-regulated kinase (ERK)-mediated MMP-9 protein expression leading to nuclear factor (NF-κB) activation by inducing the up-regulation of p21WAF1 protein expression. J. Biol. Chem. 288, 5539–5552 (2013).

    CAS  PubMed  Google Scholar 

  162. Lee, S. J. et al. Identification of pro-inflammatory cytokines associated with muscle invasive bladder cancer; the roles of IL-5, IL-20, and IL-28A. PLoS ONE 7, e40267 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Nagakawa, H. et al. Expression of interleukin-22 in murine carcinoma cells did not influence tumour growth in vivo but did improve survival of the inoculated hosts. Scand. J. Immunol. 60, 449–454 (2004).

    CAS  PubMed  Google Scholar 

  164. Wen, Z. et al. High expression of interleukin-22 and its receptor predicts poor prognosis in pancreatic ductal adenocarcinoma. Ann. Surg. Oncol. 21, 125–132 (2014).

    PubMed  Google Scholar 

  165. Lim, C. & Savan, R. The role of the IL-22/IL-22R1 axis in cancer. Cytokine Growth Factor Rev. 25, 257–271 (2014).

    CAS  PubMed  Google Scholar 

  166. Emdad, L. et al. Historical perspective and recent insights into our understanding of the molecular and biochemical basis of the antitumor properties of mda-7/IL-24. Cancer Biol. Ther. 8, 391–400 (2009).

    PubMed  Google Scholar 

  167. Whitaker, E. L., Filippov, V. A. & Duerksen-Hughes, P. J. Interleukin 24: mechanisms and therapeutic potential of an anti-cancer gene. Cytokine Growth Factor Rev. 23, 323–331 (2012).

    CAS  PubMed  Google Scholar 

  168. Kreis, S., Philippidou, D., Margue, C. & Behrmann, I. IL-24: a classic cytokine and/or a potential cure for cancer? J. Cell. Mol. Med. 16, 2505–2510 (2008).

    Google Scholar 

  169. Kreis, S. et al. Recombinant interleukin-24 lacks apoptosis-inducing properties in melanoma cells. PLoS ONE 2, e1300 (2007). This paper investigates whether IL-24 can directly elicit anticancer activity as a cytokine.

    PubMed  PubMed Central  Google Scholar 

  170. Yu, H., Pardoll, D. & Jove, R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nature Rev. Cancer 9, 798–809 (2009).

    CAS  Google Scholar 

  171. Musteanu, M. et al. Stat3 is a negative regulator of intestinal tumor progression in ApcMin mice. Gastroenterology 138, 1003–1011. e1-5 (2010).

    CAS  PubMed  Google Scholar 

  172. You, W. et al. IL-26 promotes the proliferation and survival of human gastric cancer cells by regulating the balance of STAT1 and STAT3 activation. PLoS ONE 8, e63588 (2013).

    PubMed  PubMed Central  Google Scholar 

  173. Meira, L. B. et al. DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice. J. Clin. Invest. 118, 2516–2525 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  174. Kirchberger, S. et al. Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model. J. Exp. Med. 210, 917–931 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  175. Yang, L. et al. Amelioration of high fat diet induced liver lipogenesis and hepatic steatosis by interleukin-22. J. Hepatol. 53, 339–347 (2010). This study reports the role of IL-22 in regulating lipid metabolism.

    CAS  PubMed  Google Scholar 

  176. Kanneganti, T. D. & Dixit, V. D. Immunological complications of obesity. Nature Immunol. 13, 707–712 (2012).

    CAS  Google Scholar 

  177. Inoue, H. et al. Role of STAT-3 in regulation of hepatic gluconeogenic genes and carbohydrate metabolism in vivo. Nature Med. 10, 168–174 (2004).

    CAS  PubMed  Google Scholar 

  178. Vijay-Kumar, M. et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 328, 228–231 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  179. Wang, X. et al. Interleukin-22 alleviates metabolic disorders and restores mucosal immunity in diabetes. Nature 514, 237–241 (2014). This study demonstrates that IL-22 mediates several essential functions linked to metabolic syndrome, including modulating lipid metabolism in adipose tissue and reducing food consumption.

    CAS  PubMed  Google Scholar 

  180. Hansson, G. K. Inflammation, atherosclerosis, and coronary artery disease. N. Engl. J. Med. 352, 1685–1695 (2005).

    CAS  PubMed  Google Scholar 

  181. Prodanovich, S. et al. Association of psoriasis with coronary artery, cerebrovascular, and peripheral vascular diseases and mortality. Arch. Dermatol. 145, 700–703 (2009).

    PubMed  Google Scholar 

  182. Ellison, S. et al. Attenuation of experimental atherosclerosis by interleukin-19. Arterioscler Thromb. Vasc. Biol. 33, 2316–2324 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  183. Chen, W. Y., Cheng, B. C., Jiang, M. J., Hsieh, M. Y. & Chang, M. S. IL-20 is expressed in atherosclerosis plaques and promotes atherosclerosis in apolipoprotein E-deficient mice. Arteriosclerosis, Thromb. Vascular Biol. 26, 2090–2095 (2006).

    CAS  Google Scholar 

  184. Zenewicz, L. A. et al. IL-22 deficiency alters colonic microbiota to be transmissible and colitogenic. J. Immunol. 190, 5306–5312 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  185. Gaboriau-Routhiau, V. et al. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31, 677–689 (2009).

    CAS  PubMed  Google Scholar 

  186. Ivanov, I. I. et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485–498 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  187. Wu, H.-J. et al. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32, 815–827 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  188. Lee, Y. K., Menezes, J. S., Umesaki, Y. & Mazmanian, S. K. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc. Natl Acad. Sci. USA 108 (Suppl. 1), 4615–4622 (2011).

    CAS  PubMed  Google Scholar 

  189. Qiu, J. et al. Group 3 innate lymphoid cells inhibit T-cell-mediated intestinal inflammation through aryl hydrocarbon receptor signaling and regulation of microflora. Immunity 39, 386–399 (2013).

    CAS  PubMed  Google Scholar 

  190. Upadhyay, V. et al. Lymphotoxin regulates commensal responses to enable diet-induced obesity. Nature Immunol. 13, 947–953 (2012).

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wenjun Ouyang.

Ethics declarations

Competing interests

All authors are employees of Genentech.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rutz, S., Wang, X. & Ouyang, W. The IL-20 subfamily of cytokines — from host defence to tissue homeostasis. Nat Rev Immunol 14, 783–795 (2014). https://doi.org/10.1038/nri3766

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nri3766

This article is cited by

Search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer