Environmental factors can profoundly impact the development and function of the mucosal immune system. The microbiota is one such factor that is known to regulate intestinal interleukin-17 (IL-17) producing CD4+ T helper (Th17) cells, but little is known about other environmental cues that influence their development. Here, we show that the transcription factor NFIL3 suppresses Th17 development by directly binding to the Rorγt promoter and repressing its activity. NFIL3 is linked to the circadian clock network through the transcription factor REV-ERBα, and accordingly we observed altered intestinal Th17 cell frequencies in mice that lacked REV-ERBα or were subjected to disturbed light cycles. Together, our findings reveal a new transcriptional regulatory network that regulates intestinal Th17 cell differentiation and unveil a molecular link between the circadian clock circuitry and Th17 cell development.
- Copyright © 2013 by The American Association of Immunologists, Inc.