The TNF family member TL1A induces IL-22 secretion in committed human Th17 cells via IL-9 induction. Issue 3 (12th October 2016)

• Record Type: Journal Article
• Authors: Thomas, Lisa S; Targan, Stephan R; Tsuda, Masato; Yu, Qi T; Salumbides, Brenda C; Haritunians, Talin; Mengesha, Emebet; McGovern, Dermot P B; Michelsen, Kathrin S
• Is Part Of: Journal of leukocyte biology. Volume 101:Issue 3(2017)
• Page Start: 727
• Page End: 737
• Publication Date: 2016-10-12
• Subjects: cytokines -- inflammation -- T-helper cell responses; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.3A0316-129R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Mechanism identified by which TL1A differentially regulates the expression of TH17 effector cytokines IL-17 and IL-22, in human TH17 cells. Abstract: TL1A contributes to the pathogenesis of several chronic inflammatory diseases, including those of the bowel by enhancing TH 1, TH 17, and TH 2 responses. TL1A mediates a strong costimulation of these TH subsets, particularly of mucosal CCR9 + T cells. However, the signaling pathways that TL1A induces in different TH subsets are incompletely understood. We investigated the function of TL1A on human TH 17 cells. TL1A, together with TGF-β, IL-6, and IL-23, enhanced the secretion of IL-17 and IFN-γ 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-γ. In contrast, TL1A alone induced high levels of IL-22 in memory CD4 + T cells and committed TH 17 cells. However, TL1A did not enhance expression of IL-17A in TH 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 TH 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 TH 17 cells isolated from patients with Crohn's disease. These data suggest that TL1A differentially induces expression of TH 17 effector cytokines IL-17, -9, and -22 and provides a potential target for therapeutic intervention in TH 17-driven chronic inflammatory diseases.