The TNF family member TL1A induces IL-22 secretion in committed human Th 17 cells via IL-9 induction
| Autor: | Masato Tsuda, Lisa S. Thomas, Talin Haritunians, Stephan R. Targan, Brenda C. Salumbides, Emebet Mengesha, Kathrin S. Michelsen, Qi T. Yu, Dermot P.B. McGovern |
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| Rok vydání: | 2016 |
| Předmět: |
Tumor Necrosis Factor Ligand Superfamily Member 15
0301 basic medicine Immunology Inflammation Cell Separation Biology Interleukin 22 Interferon-gamma 03 medical and health sciences Crohn Disease BATF medicine Humans Immunology and Allergy Interferon gamma Secretion Interleukin 9 Inflammation Extracellular Mediators & Effector Molecules Gene Expression Profiling Interleukins Interleukin-9 Cell Biology Aryl hydrocarbon receptor Cell biology 030104 developmental biology biology.protein Leukocyte Common Antigens Th17 Cells medicine.symptom Signal transduction Immunologic Memory medicine.drug |
| Zdroj: | Journal of Leukocyte Biology. 101:727-737 |
| ISSN: | 1938-3673 0741-5400 |
| Popis: | 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 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 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. |
| Databáze: | OpenAIRE |
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