TL1A-DR3 interaction regulates Th17 cell function and Th17-mediated autoimmune disease.
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.
Pappu
Bhanu P
BP
Department of Immunology, MD Anderson Cancer Center, Houston, TX 77030, USA.
Borodovsky
Anna
A
Zheng
Timothy S
TS
Yang
Xuexian
X
Wu
Ping
P
Dong
Xingwen
X
Weng
Shawn
S
Browning
Beth
B
Scott
Martin L
ML
Ma
Li
L
Su
Lihe
L
Tian
Qiang
Q
Schneider
Pascal
P
Flavell
Richard A
RA
Dong
Chen
C
Burkly
Linda C
LC
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D001921:Brain / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation; D002455:Cell Division; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D015803:HLA-DR3 Antigen / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
D016207:Cytokines; D017931:DNA Primers; D015803:HLA-DR3 Antigen; C505947:Tnfsf15 protein, mouse; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15