[HTML][HTML] Transcription factor IRF8 directs a silencing programme for TH17 cell differentiation

X Ouyang, R Zhang, J Yang, Q Li, L Qin, C Zhu… - Nature …, 2011 - nature.com
X Ouyang, R Zhang, J Yang, Q Li, L Qin, C Zhu, J Liu, H Ning, MS Shin, M Gupta, CF Qi…
Nature communications, 2011nature.com
TH17 cells are recognized as a unique subset of T helper cells that have critical roles in the
pathogenesis of autoimmunity and tissue inflammation. Although RORγt is necessary for the
generation of TH17 cells, the molecular mechanisms underlying the functional diversity of
TH17 cells are not fully understood. Here we show that a member of interferon regulatory
factor (IRF) family of transcription factors, IRF8, has a critical role in silencing TH17-cell
differentiation. Mice with a conventional knockout, as well as a T cell-specific deletion, of the …
Abstract
TH17 cells are recognized as a unique subset of T helper cells that have critical roles in the pathogenesis of autoimmunity and tissue inflammation. Although RORγt is necessary for the generation of TH17 cells, the molecular mechanisms underlying the functional diversity of TH17 cells are not fully understood. Here we show that a member of interferon regulatory factor (IRF) family of transcription factors, IRF8, has a critical role in silencing TH17-cell differentiation. Mice with a conventional knockout, as well as a T cell-specific deletion, of the Irf8 gene exhibited more efficient TH17 cells. Indeed, studies of an experimental model of colitis showed that IRF8 deficiency resulted in more severe inflammation with an enhanced TH17 phenotype. IRF8 was induced steadily and inhibited TH17-cell differentiation during TH17 lineage commitment at least in part through its physical interaction with RORγt. These findings define IRF8 as a novel intrinsic transcriptional inhibitor of TH17-cell differentiation.
nature.com