Mini-reviewThe paradoxical role of IL-10 in immunity and cancer
Introduction
Interleukin-10 (IL-10) is a cytokine isolated and characterized around 1990 [1], [2]. It is originally named as cytokine synthesis inhibitory factor (CSIF). Presently, IL-10 is the main member of the IL-10 superfamily which also includes IL-19, IL-20, IL-22, IL-24, IL-26 as well as type III IFN-γ subfamily. IL-10 is secreted by a wide variety of cell types including macrophages and T cell subsets [3], [4], [5], [6], [7], [8], [9]. IL-10 has been the subject of intense study due to its pleiotropic and at times seemingly contradictory effects. The ultimate effects of IL-10 vary greatly depending on both the experimental context and the cell types under investigation. This review aims to summarize the controversial functions of IL-10 in immunology as well as in the pathogenesis of tumor.
Section snippets
The production and the regulation of expression of IL-10
Human IL-10 has 178 aa in total, with a 160 aa mature segment and an 18 aa signal sequence. IL-10 is a V-shaped homodimer with a molecular weight of 37 kDa. Many types of cells could produce IL-10, including monocytes/macrophages, DCs, B cells, various T regulatory cell subsets, CD4+ and CD8+ T cells and natural killer (NK) cells [3], [6]. The regulation of IL-10 expression seems complex. IL-10 expression could be regulated at two levels: transcription level and post-transcription level. It has
The IL-10 receptor (IL-10R) and signaling pathway
The binding constant (KD) for the ligand binding subunit of IL-10R (designated IL-10R1) is 35–200 pM and has a mass of 90–120 kDa [15]. Interestingly, although the murine and human IL-10R1s are 60% identical and 73% similar [16], the murine version of the receptor binds both murine and human IL-10, while the human version of the receptor is species specific [15], which is important in the context of research since much of the current knowledge has come from experiments using mIL-10, mIL-10R, or
Cytotoxic T lymphocytes (CTLs)
When administered in combination with IL-4 and/or IL-2, IL-10 stimulates proliferation of mature murine CD8+ T cells in vitro [28]. In addition to these findings, the experimenters also found that IL-10 in combination with IL-2 increased the cytolytic activity of the T cells. Other findings have corroborated the co-stimulatory effects of IL-10 on CD8+ T cells when administered in vitro with IL-2 and demonstrated that the proliferation of human papilloma virus-specific CTLs was increased by the
IL-10 and cancer
The role of IL-10 in tumor pathogenesis and development is extremely controversial to this point. Some studies indicate that IL-10 positively contributes to tumor growth and promotion, whereas other studies have shown that it contributes to the eradication and suppression of angiogenesis and metastasis necessary for long term patient survival.
Summary and future direction
IL-10 is produced by a wide-variety of cells and it is a highly pleiotropic cytokine. Its role in tumorigenesis and development is still controversial. One explanation for the degree of conflicting evidence and opinion regarding the role of IL-10 in cancer is the balance of cytokines and possibly other conditions in the tissue that so delicately controls its function in different cell types. It is also possible that IL-10 might play a dual role in tumorigenesis and development. As cancer begins
Conflict of interest
The authors have no conflict of interest.
Acknowledgments
This study was supported by a grant from Des Moines University for Yujiang Fang.
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