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TL1A–DR3 interaction regulates Th17 cell function and Th17-mediated autoimmune disease

  • Pappu, Bhanu P. Department of Immunology, M.D. Anderson Cancer Center, Houston, TX 77030
  • Borodovsky, Anna Department of Immunobiology and Drug Discovery, Biogen Idec, Cambridge, MA 02142
  • Zheng, Timothy S. Department of Immunobiology and Drug Discovery, Biogen Idec, Cambridge, MA 02142
  • Yang, Xuexian Department of Immunology, M.D. Anderson Cancer Center, Houston, TX 77030
  • Wu, Ping Department of Immunobiology and Drug Discovery, Biogen Idec, Cambridge, MA 02142
  • Dong, Xingwen Department of Immunobiology and Drug Discovery, Biogen Idec, Cambridge, MA 02142
  • Weng, Shawn Department of Immunobiology and Drug Discovery, Biogen Idec, Cambridge, MA 02142
  • Browning, Beth Department of Immunobiology and Drug Discovery, Biogen Idec, Cambridge, MA 02142
  • Scott, Martin L. Department of Immunobiology and Drug Discovery, Biogen Idec, Cambridge, MA 02142
  • Ma, Li Institute for Systems Biology, Seattle, WA 98103
  • Su, Lihe Department of Immunobiology and Drug Discovery, Biogen Idec, Cambridge, MA 02142
  • Tian, Qiang Institute for Systems Biology, Seattle, WA 98103
  • Schneider, Pascal Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland
  • Flavell, Richard A. Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520
  • Dong, Chen Department of Immunology, M.D. Anderson Cancer Center, Houston, TX 77030
  • Burkly, Linda C. Department of Immunobiology and Drug Discovery, Biogen Idec, Cambridge, MA 02142
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  • 2008-4-14
Published in:
  • Journal of Experimental Medicine. - Rockefeller University Press. - 2008, vol. 205, no. 5, p. 1049-1062
Immunology
Immunology and Allergy
English T helper type 17 (Th17) cells play an important pathogenic function in autoimmune diseases; their regulation, however, is not well understood. We show that the expression of a tumor necrosis factor receptor family member, death receptor 3 (DR3; also known as TNFRSF25), is selectively elevated in Th17 cells, and that TL1A, its cognate ligand, can promote the proliferation of effector Th17 cells. To further investigate the role of the TL1A–DR3 pathway in Th17 regulation, we generated a TL1A-deficient mouse and found that TL1A−/− dendritic cells exhibited a reduced capacity in supporting Th17 differentiation and proliferation. Consistent with these data, TL1A−/− animals displayed decreased clinical severity in experimental autoimmune encephalomyelitis (EAE). Finally, we demonstrated that during EAE disease progression, TL1A was required for the optimal differentiation as well as effector function of Th17 cells. These observations thus establish an important role of the TL1A–DR3 pathway in promoting Th17 cell function and Th17-mediated autoimmune disease.
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  • English
Open access status
hybrid
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https://sonar.ch/global/documents/46462
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