TL1A contributes to the pathogenesis of several chronic inflammatory diseases, including those of the bowel by enhancing T(H)1, T(H)17, and T(H)2 responses. TL1A mediates a strong costimulation of these T-H subsets, particularly of mucosal CCR9(+) T cells. However, the signaling pathways that TL1A induces in different T-H subsets are incompletely understood. We investigated the function of TL1A on human T(H)17 cells. TL1A, together with TGF-, IL-6, and IL-23, enhanced the secretion of IL-17 and IFN- from human CD4(+) memory T cells. TL1A induced expression of the transcription factors BATF and T-bet that correlated with the secretion of IL-17 and IFN-. In contrast, TL1A alone induced high levels of IL-22 in memory CD4(+) T cells and committed T(H)17 cells. However, TL1A did not enhance expression of IL-17A in T(H)17 cells. Expression of the transcription factor aryl hydrocarbon receptor, which regulates the expression of IL-22 was not affected by TL1A. Transcriptome analysis of T(H)17 cells revealed increased expression of IL-9 in response to TL1A. Blocking IL-9 receptor antibodies abrogated TL1A-induced IL-22 secretion. Furthermore, TL1A increased IL-9 production by peripheral T(H)17 cells isolated from patients with Crohn's disease. These data suggest that TL1A differentially induces expression of T(H)17 effector cytokines IL-17, -9, and -22 and provides a potential target for therapeutic intervention in T(H)17-driven chronic inflammatory diseases.