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A neuronal receptor, neuropilin-1, is essential for the initiation of the primary immune response

A Corrigendum to this article was published on 01 April 2003

Abstract

The initiation of a primary immune response requires contact between dendritic cells (DCs) and resting T cells. However, little is known about the proteins that mediate this initial contact. We show here that neuropilin-1, a receptor involved in axon guidance, was expressed by human DCs and resting T cells both in vitro and in vivo. The initial contact between DCs and resting T cells led to neuropilin-1 polarization on T cells. DCs and resting T cells specifically bound soluble neuropilin-1, and resting T cells formed clusters with neuropilin-1–transfected COS-7 cells in a neuropilin-1–dependent manner. Functionally, preincubation of DCs or resting T cells with blocking neuropilin-1 antibodies inhibited DC-induced proliferation of resting T cells. These data suggest that neuropilin-1 mediates interactions between DCs and T cells that are essential for initiation of the primary immune response and show parallels between the nervous and immune systems.

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Figure 1: Neuropilin-1 is expressed by in vitro human monocyte-derived DCs.
Figure 2: Expression of neuropilin-1 in human lymphoid tissues.
Figure 3: Neuropilin-1 is expressed by resting T cells and T cell–DC interaction induces neuropilin-1 polarization.
Figure 4: Adhesion of soluble neuropilin-1 to DCs and T cells.
Figure 5: Heterotypic T cell clustering with neuropilin-1–expressing COS-7 cells.
Figure 6: Neuropilin-1 mediates DC–T cell clustering and DC-induced proliferation of resting T cells.

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References

  1. Banchereau, J. & Steinman, R.M. Dendritic cells and the control of immunity Nature 392, 245–252 (1998).

    Article  CAS  Google Scholar 

  2. Dustin, M.L. & Cooper, J.A. The immunological synapse and the actin cytoskeleton: molecular hardware for T cell signaling. Nature Immunol. 1, 23–29 (2000).

    Article  CAS  Google Scholar 

  3. Al-Alwan, M.M., Rowden, G., Lee, T.D. & West, K.A. The dendritic cell cytoskeleton is critical for the formation of the immunological synapse. J. Immunol. 166, 1452–1456 (2001).

    Article  CAS  Google Scholar 

  4. Langerhans, P. Uber die Nerven der menschlichen Haut. Virchows Arch. path. Anat. 44, 325–337 (1868).

    Article  Google Scholar 

  5. Semaphorin Nomenclature Committee Unified nomenclature for the semaphorins/collapsins. Cell 97, 551–552 (1999).

  6. Kolodkin, A.L. . et al. Neuropilin is a semaphorin III receptor. Cell 90, 753–762 (1997).

    Article  CAS  Google Scholar 

  7. He, Z. & Tessier-Lavigne, M. Neuropilin is a receptor for the axonal chemorepellent semaphorin III. Cell 90, 739–751 (1997).

    Article  CAS  Google Scholar 

  8. Kolodkin, A.L., Matthes, D.J. & Goodman, C.S. The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules. Cell 75, 1389–1399 (1993).

    Article  CAS  Google Scholar 

  9. Kolodkin, A.L. Semaphorin-mediated neuronal growth cone guidance. Prog. Brain Res. 117, 115–132 (1998).

    Article  CAS  Google Scholar 

  10. Yu, H.H. & Kolodkin, A.L. Semaphorin signaling: a little less per-plexin. Neuron 22, 11–14 (1999).

    Article  CAS  Google Scholar 

  11. Takahashi, T. & Strittmatter, S.M. Plexina1 autoinhibition by the plexin sema domain. Neuron 29, 429–439 (2001).

    Article  CAS  Google Scholar 

  12. Tordjman, R. . et al. Neuropilin-1 is expressed on bone marrow stromal cells: a novel interaction with hematopoietic cells? Blood 94, 2301–2309 (1999).

    CAS  PubMed  Google Scholar 

  13. Soker, S., Takashima, S., Miao, H.Q., Neufeld, G. & Klagsbrun, M. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform- specific receptor for vascular endothelial growth factor. Cell 92, 735–745 (1998).

    Article  CAS  Google Scholar 

  14. Gagnon, M.L. . et al. Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: In vivo expression and antitumor activity. Proc. Natl. Acad. Sci. USA 97, 2573–2578 (2000).

    Article  CAS  Google Scholar 

  15. Geissmann, F. . et al. Transforming growth factor β1, in the presence of granulocyte/macrophage colony-stimulating factor and interleukin 4, induces differentiation of human peripheral blood monocytes into dendritic Langerhans cells. J. Exp. Med. 187, 961–966 (1998).

    Article  CAS  Google Scholar 

  16. Krenacs, L., Tiszalvicz, L., Krenacs, T. & Boumsell, L. Immunohistochemical detection of CD1A antigen in formalin-fixed and paraffin-embedded tissue sections with monoclonal antibody 010. J. Pathol. 171, 99–104 (1993).

    Article  CAS  Google Scholar 

  17. Leupin, O., Zaru, R., Laroche, T., Muller, S. & Valitutti, S. Exclusion of CD45 from the T-cell receptor signaling area in antigen- stimulated T lymphocytes. Curr. Biol. 10, 277–280 (2000).

    Article  CAS  Google Scholar 

  18. Revy, P., Sospedra, M., Barbour, B. & Trautmann, A. Functional antigen-independent synapses formed between T cells and dendritic cells. Nature Immunol. 2, 925–931 (2001).

    Article  CAS  Google Scholar 

  19. Chen, H., Chedotal, A., He, Z., Goodman, C.S. & Tessier-Lavigne, M., 2, a novel member of the neuropilin family, is a high affinity receptor for the semaphorins Sema E and Sema IV but not Sema III. Neuron 19, 547–559 (1997).

    Article  CAS  Google Scholar 

  20. Chen, H., He, Z., Bagri, A. & Tessier-Lavigne, M. Semaphorin-neuropilin interactions underlying sympathetic axon responses to class III semaphorins. Neuron 21, 1283–1290 (1998).

    Article  CAS  Google Scholar 

  21. Geijtenbeek, T.B. . et al. Identification of a DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell 100, 575–585 (2000).

    Article  CAS  Google Scholar 

  22. Delemarre, F.G., Hoogeveen, P.G., De Haan-Meulman, M., Simons, P.J. & Drexhage, H.A. Homotypic cluster formation of dendritic cells, a close correlate of their state of maturation. Defects in the biobreeding diabetes-prone rat. J. Leukoc. Biol. 69, 373–380 (2001).

    CAS  PubMed  Google Scholar 

  23. Song, H. . et al. Conservation of neuronal growth cone responses from repulsion to attraction by cyclic nucleotides. Science 281, 1515–1518 (1998).

    Article  CAS  Google Scholar 

  24. Castellani, V., Chedotal, A., Schachner, M., Faivre-Sarrailh, C. & Rougon, G. Analysis of the L1-deficient mouse phenotype reveals cross-talk between Sema3A and L1 signaling pathways in axonal guidance. Neuron 27, 237–249 (2000).

    Article  CAS  Google Scholar 

  25. Khan, A.A., Bose, C., Yam, L.S., Soloski, M.J. & Rupp, F. Physiological regulation of the immunological synapse by agrin. Science 292, 1681–1686 (2001).

    Article  CAS  Google Scholar 

  26. Wu, J.Y. et al. The neuronal repellent Slit inhibits leukocyte chemotaxis induced by chemotactic factors. Nature 410, 948–952 (2001).

    Article  CAS  Google Scholar 

  27. Cordell, J.L. . et al. Immunoenzymatic labelling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J. Histochem. Cytochem. 32, 219–229 (1984).

    Article  CAS  Google Scholar 

  28. Tordjman, R. . et al. Erthroblasts are a source of angiogenic factors. Blood 97, 1968–1974 (2001).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank M. Tessier-Lavigne and Z. He for the gift of the NP-1 construct and of anti–neuropilin-1 (intracytoplasmic and blocking anti–neuropilin-1); A. Amara for the gift of anti-DC-SIGN; A. Trautmann, G. Bismuth and A. Chédotal for their advice; and A. Baruchel for his advice and encouragement. Supported by the INSERM, the CNRS and the Association pour la Recherche sur le Cancer(grant number 5715). M. C. was supported by the Fondation pour la Recherche Médicale.

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Correspondence to Rafaèle Tordjman or Olivier Hermine.

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Tordjman, R., Lepelletier, Y., Lemarchandel, V. et al. A neuronal receptor, neuropilin-1, is essential for the initiation of the primary immune response. Nat Immunol 3, 477–482 (2002). https://doi.org/10.1038/ni789

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