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

TitleTL1A-DR3 interaction regulates Th17 cell function and Th17-mediated autoimmune disease
Publication TypeJournal Article
Year of Publication2008
AuthorsPappu BP, Borodovsky A, Zheng TS, Yang X, Wu P, Dong X, Weng S, Browning B, Scott ML, Ma L, Su L, Tian Q, Schneider P, Flavell RA, Dong C, Burkly LC
JournalJ Exp Med
Volume205
Pagination1049-62
Date PublishedMay 12
PubMed Central ID2373838
PMID18411337
Keywords15/*deficiency/genetics/physiology, Animals, Autoimmune Diseases/*immunology, Brain/immunology/pathology, Cell Differentiation, Cell Division, Cytokines/metabolism, DNA Primers, Encephalomyelitis, Autoimmune, Experimental/*immunology, Female, HLA-DR3 Antigen/*immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, Spinal Cord/immunology/pathology, T-Lymphocytes, Regulatory/cytology/immunology, T-Lymphocytes/cytology/immunology, Tumor Necrosis Factor Ligand Superfamily Member
AbstractT 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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