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Title:
Induction and molecular signature of pathogenic TH17 cells | Nature Immunology
Description:
Exposure to interleukin 23 (IL-23) is required for the induction of pathogenic TH17 cells. Kuchroo and colleagues show that IL-23-dependent induction of the cytokine TGF-β3 produces a molecular signature characteristic of highly pathogenic TH17 cells. Interleukin 17 (IL-17)-producing helper T cells (TH17 cells) are often present at the sites of tissue inflammation in autoimmune diseases, which has led to the conclusion that TH17 cells are main drivers of autoimmune tissue injury. However, not all TH17 cells are pathogenic; in fact, TH17 cells generated with transforming growth factor-β1 (TGF-β1) and IL-6 produce IL-17 but do not readily induce autoimmune disease without further exposure to IL-23. Here we found that the production of TGF-β3 by developing TH17 cells was dependent on IL-23, which together with IL-6 induced very pathogenic TH17 cells. Moreover, TGF-β3-induced TH17 cells were functionally and molecularly distinct from TGF-β1-induced TH17 cells and had a molecular signature that defined pathogenic effector TH17 cells in autoimmune disease.
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nature portfolio permissions reprints stem cell research privacy policy advertising transforming growth factor-β1 transforming growth factors-β1 social media th17 cell-derived tgf-β1 disrupted ifn-gamma gene tgf-β1-induced th17 cells gene-expression data tgf-β3-induced th17 cells india pertussis toxin-induced inhibition wnt/β-catenin signaling loxp-flanked tgfb3 alleles nature 383 nature 441 nature 453 nature 421 nature 475 nature 467 nature 484 nature aryl hydrocarbon receptor microarray expression data central nervous system il-7rα confers susceptibility experimental autoimmune encephalomyelitis tissue-specific expression autoimmune tissue injury permissions springerlink instant access ifn-γ tgf-β signaling transcription factor gata-3 t-bet regulates tgf-β signalling interleukin-23 receptor variants tissue inflammation pathogenic effector th17 privacy personal data development competing financial interests cytokine gm-csf il-6 produce il-17 pathogenic th17 cells interleukin 17–producing effector
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