A role for BATF3 in T(H)9 differentiation and T cell driven mucosal pathologies

T helper 9 (T(H)9) cells are important for the development of inflammatory and allergic diseases. The T(H)9 transcriptional network converge signals from cytokines and antigen presentation but is incompletely understood. Here, we identified TL1A, a member of the TNF superfamily, as strong inducer of mouse and human T(H)9 differentiation. Mechanistically, TL1A induced the expression of the transcription factors BATF and BATF3 and facilitated their binding to the Il9 promoter leading to enhanced secretion of IL-9. BATF- and BATF3-deficiencies impaired IL-9 secretion under T(H)9 and T(H)9-TL1A polarizing conditions. In vivo, using a T cell transfer model we demonstrated that TL1A promoted IL-9-dependent, T(H)9 cell-induced intestinal and lung inflammation. Neutralizing IL-9 antibodies attenuated TL1A-driven mucosal inflammation. Batf3(−/−) T(H)9-TL1A cells induced reduced inflammation and cytokine expression in vivo compared to WT cells. Our results demonstrate that TL1A promotes T(H)9 cell differentiation and function and define a role of BATF3 in T cell driven mucosal inflammation.