TL1A–DR3 interaction regulates Th17 cell function and Th17-mediated autoimmune disease
| Autor: | Bhanu P. Pappu, Xuexian O. Yang, Shawn Weng, Ping Wu, Qiang Tian, Richard A. Flavell, Beth Browning, Timothy S. Zheng, Xingwen Dong, Martin L. Scott, Lihe Su, Chen Dong, Li Ma, Linda C. Burkly, Anna Borodovsky, Pascal Schneider |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Tumor Necrosis Factor Ligand Superfamily Member 15
Animals Autoimmune Diseases Brain Cell Differentiation Cell Division Cytokines DNA Primers Encephalomyelitis Autoimmune Experimental Female HLA-DR3 Antigen Mice Mice Inbred C57BL Mice Knockout Spinal Cord T-Lymphocytes T-Lymphocytes Regulatory Cell division medicine.medical_treatment Cellular differentiation Immunology Biology Article medicine Immunology and Allergy Autoimmune disease Effector Experimental autoimmune encephalomyelitis hemic and immune systems Articles medicine.disease Ligand (biochemistry) Cell biology Cytokine Death receptor 3 |
| Zdroj: | The Journal of Experimental Medicine Journal of Experimental Medicine, vol. 205, no. 5, pp. 1049-1062 |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20071364 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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