title: The TNF family member TL1A induces IL-22 secretion in committed human Th17 cells via IL-9 induction.
abstract: TL1A contributes to the pathogenesis of several chronic inflammatory diseases, including those of the bowel by enhancing TH1, TH17, and TH2 responses. TL1A mediates a strong costimulation of these THsubsets, particularly of mucosal CCR9+T cells. However, the signaling pathways that TL1A induces in different THsubsets are incompletely understood. We investigated the function of TL1A on human TH17 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 TH17 cells. However, TL1A did not enhance expression of IL-17A in TH17 cells. Expression of the transcription factor aryl hydrocarbon receptor, which regulates the expression of IL-22 was not affected by TL1A. Transcriptome analysis of TH17 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 TH17 cells isolated from patients with Crohn's disease. These data suggest that TL1A differentially induces expression of TH17 effector cytokines IL-17, -9, and -22 and provides a potential target for therapeutic intervention in TH17-driven chronic inflammatory diseases.
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Thomas
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Targan
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Masato
authors.initials: M
authors.lastname: Tsuda
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Qi T
authors.initials: QT
authors.lastname: Yu
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Brenda C
authors.initials: BC
authors.lastname: Salumbides
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Talin
authors.initials: T
authors.lastname: Haritunians
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Emebet
authors.initials: E
authors.lastname: Mengesha
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Dermot P B
authors.initials: DP
authors.lastname: McGovern
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA kathrin.michelsen@cshs.org.
authors.forename: Kathrin S
authors.initials: KS
authors.lastname: Michelsen
mesh_terms: D002469:Cell Separation; D003424:Crohn Disease / Q000276:immunology / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D016906:Interleukin-9 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D058504:Th17 Cells / Q000378:metabolism*; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000378:metabolism*; D000097043:Interleukin-22
chemical_list: D007371:Interferon-gamma; D016906:Interleukin-9; D007378:Interleukins; D017493:Leukocyte Common Antigens; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D000097043:Interleukin-22
keywords: T-helper cell responses; cytokines; inflammation