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Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease
Abstract
Activation of naive CD4(+) T-helper cells results in the development of at least two distinct effector populations, Th1 and Th2 cells. Th1 cells produce cytokines (interferon (IFN)-gamma, interleukin (IL)-2, tumour-necrosis factor (TNF)-alpha and lymphotoxin) that are commonly associated with cell-mediated immune responses against intracellular pathogens, delayed-type hypersensitivity reactions, and induction of organ-specific autoimmune diseases. Th2 cells produce cytokines (IL-4, IL-10 and IL-13) that are crucial for control of extracellular helminthic infections and promote atopic and allergic diseases. Although much is known about the functions of these two subsets of T-helper cells, there are few known surface molecules that distinguish between them. We report here the identification and characterization of a transmembrane protein, Tim-3, which contains an immunoglobulin and a mucin-like domain and is expressed on differentiated Th1 cells. In vivo administration of antibody to Tim-3 enhances the clinical and pathological severity of experimental autoimmune encephalomyelitis (EAE), a Th1-dependent autoimmune disease, and increases the number and activation level of macrophages. Tim-3 may have an important role in the induction of autoimmune diseases by regulating macrophage activation and/or function.
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“TIM-3 protein is highly conserved between mice and humans68, including the intracellular domain, which we found is required for TIM-3 to bind SMAD2 (Fig. 3a–c).”
From Immune checkpoint TIM-3 regulates microglia and Alzheimer’s disease (2025) · cites this paper as [68]
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Identification of Tapr (an airway hyperreactivity regulatory locus) and the linked Tim gene family
McIntire, J. J., Umetsu, S. E., Akbari, O., Potter, M., Kuchroo, V. K., Barsh, G. S., Freeman, G. J., Umetsu, D. T., & DeKruyff, R. H. (2001) · Nature Immunology · doi:10.1038/ni739 · Cited by 501
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Research works printed but not linked: 23
- Mosmann, T. R., Cherwinski, H., Bond, M. W., Giedlin, M. A. & Coffman, R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 136, 2348–2357 (1986). · DOI
- Mosmann, T. R. & Sad, S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol. Today 17, 138–146 (1996). · DOI
- Abbas, A. K., Murphy, K. M. & Sher, A. Functional diversity of helper T lymphocytes. Nature 383, 787–793 (1996). · DOI
- Sher, A. & Coffman, R. L. Regulation of immunity to parasites by T cells and T cell-derived cytokines. Annu. Rev. Immunol. 10, 385–409 (1992). · DOI
- Liblau, R. S., Singer, S. M. & McDevitt, H. O. Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases. Immunol. Today 16, 34–38 (1995). · DOI
- Syrbe, U., Siveke, J. & Hamann, A. Th1/Th2 subsets: distinct differences in homing and chemokine receptor expression? Springer Semin. Immunopathol. 21, 263–285 (1999). · DOI
- Kuchroo, V. K. et al. B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: application to autoimmune disease therapy. Cell 80, 707–718 (1995). · DOI
- Nicholson, L. B., Greer, J. M., Sobel, R. A., Lees, M. B. & Kuchroo, V. K. An altered peptide ligand mediates immune deviation and prevents autoimmune encephalomyelitis. Immunity 3, 397–405 (1995). · DOI
- Lack, G. et al. Nebulized but not parenteral IFN-γ decreases IgE production and normalizes airways function in a murine model of allergen sensitization. J. Immunol. 152, 2546–2554 (1994). · DOI
- Hofstra, C. L. et al. Prevention of Th2-like cell responses by coadministration of IL-12 and IL-18 is associated with inhibition of antigen-induced airway hyperresponsiveness, eosinophilia, and serum IgE levels. J. Immunol. 161, 5054–5060 (1998). · DOI
- Loetscher, P. et al. CCR5 is characteristic of Th1 lymphocytes. Nature 391, 344–345 (1998). · DOI · Paper page
- Bonecchi, R. et al. Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J. Exp. Med. 187, 129–134 (1998). · DOI
- Sallusto, F., Lenig, D., Mackay, C. R. & Lanzavecchia, A. Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes. J. Exp. Med. 187, 875–883 (1998). · DOI
- Venkataraman, C., Schaefer, G. & Schindler, U. Cutting edge: Chandra, a novel four-transmembrane domain protein differentially expressed in helper type 1 lymphocytes. J. Immunol. 165, 632–636 (2000). · DOI
- Jourdan, P. et al. IL-4 induces functional cell-surface expression of CXCR4 on human T cells. J. Immunol. 160, 4153–4157 (1998). · DOI
- Zingoni, A. et al. The chemokine receptor CCR8 is preferentially expressed in Th2 but not Th1 cells. J. Immunol. 161, 547–551 (1998). · DOI · Paper page
- McAdam, A. J. et al. Mouse inducible costimulatory molecule (ICOS) expression is enhanced by CD28 costimulation and regulates differentiation of CD4+ T cells. J. Immunol. 165, 5035–5040 (2000). · DOI
- Lohning, M. et al. T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function. Proc. Natl Acad. Sci. USA 95, 6930–6935 (1998). · DOI
- Waldner, H., Whitters, M. J., Sobel, R. A., Collins, M. & Kuchroo, V. K. Fulminant spontaneous autoimmunity of the central nervous system in mice transgenic for the myelin proteolipid protein-specific T cell receptor. Proc. Natl Acad. Sci. USA 97, 3412–3417 (2000). · DOI
- Seed, B. & Aruffo, A. Molecular cloning of the CD2 antigen, the T-cell erythrocyte receptor, by a rapid immunoselection procedure. Proc. Natl Acad. Sci. USA 84, 3365–3369 (1987). · DOI
- Gordon, E. J., Myers, K. J., Dougherty, J. P., Rosen, H. & Ron, Y. Both anti-CD11a (LFA-1) and anti-CD11b (MAC-1) therapy delay the onset and diminish the severity of experimental autoimmune encephalomyelitis. J. Neuroimmunol. 62, 153–160 (1995). · DOI
- Tran, E. H., Hoekstra, K., van Rooijen, N., Dijkstra, C. D. & Owens, T. Immune invasion of the central nervous system parenchyma and experimental allergic encephalomyelitis, but not leukocyte extravasation from blood, are prevented in macrophage-depleted mice. J. Immunol. 161, 3767–3775 (1998). · DOI
- Kohler, G. & Milstein, C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256, 495–497 (1975). · DOI
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Self-citation
Metadata
- Authors
- Monney, L., Sabatos, C. A., Gaglia, J. L., Ryu, A., Waldner, H., Chernova, T., Manning, S., Greenfield, E. A., Coyle, A. J., Sobel, R. A., Freeman, G. J., & Kuchroo, V. K.
- Venue
- Nature
- Published
- 2002-01
- Volume
- 415
- Issue
- 6871
- Pages
- 536-541
- ISSN
- 0028-0836
- 1476-4687
- Cited by
- 1,472
- References
- 1
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
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- Monney, L., Sabatos, C. A., Gaglia, J. L., Ryu, A., Waldner, H., Chernova, T., Manning, S., Greenfield, E. A., Coyle, A. J., Sobel, R. A., Freeman, G. J., & Kuchroo, V. K. (2002). Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature. https://doi.org/10.1038/415536a
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