The TNF family member TL1A induces IL-22 secretion in committed human T h 17 cells via IL-9 induction.

Autor: Thomas LS; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA., Targan SR; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA., Tsuda M; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA., Yu QT; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA., Salumbides BC; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA., Haritunians T; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA., Mengesha E; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA., McGovern DP; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA., Michelsen KS; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA kathrin.michelsen@cshs.org.
Jazyk: angličtina
Zdroj: Journal of leukocyte biology [J Leukoc Biol] 2017 Mar; Vol. 101 (3), pp. 727-737. Date of Electronic Publication: 2016 Oct 12.
DOI: 10.1189/jlb.3A0316-129R
Abstrakt: 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-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 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.
(© Society for Leukocyte Biology.)
Databáze: MEDLINE
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