IRF4 regulates IL-17A promoter activity and controls RORγt-dependent Th17 colitis in vivo

Abstract

IRF4 can directly bind to the IL-17 promotor and induces mucosal RORγt levels and IL-17 gene expression thereby controlling Th17-dependent colitis. Targeting of this molecular mechanism may lead to novel therapeutic approaches in human IBD.

Opposite Effects of Interferon Regulatory Factor 1 and Osteopontin on the Apoptosis of Epithelial Cells Induced by TNF-α in Inflammatory Bowel Disease

“…A recent study concluded that there was no obvious change in IRF1 expression in patients compared with controls. 16 However, another study observed increased expression of IRF1 in 72% of patients with CD among study cohorts. 17 Still, little is known about how IRF1 interacts with multiple cytokines and activates different signaling pathways in the context of IBD.…”

Ikaros Sets the Potential for Th17 Lineage Gene Expression through Effects on Chromatin State in Early T Cell Development

“…Among these are signals downstream of antigen-induced TCR activation that induce expression of the transcription factors IRF4 and Runx1 (14,15). IL-6 activates STAT3, which together with Runx1 and IRF4 promotes ROR␥t transcription (15)(16)(17)(18). TGF␤ signaling through SMAD2 also contributes to Runx1 induction as well as to expression of the ligand-activated transcription factor aryl hydrocarbon receptor (AhR), which is directly implicated in Il17a and Il22 transcription (9,15,19,20).…”

Tumor Necrosis Factor α-Mediated Induction of Interleukin 17C in Human Keratinocytes Is Controlled by Nuclear Factor κB

“…However, recently IB, a nuclear IB family member, was demonstrated to increase IL-17A expression by binding directly to the regulatory region of the IL-17A gene (41). In addition, the transcription factor IFN regulatory factor 4 has been described to directly bind to the IL-17A promoter and thereby regulate the expression of IL-17A (42).…”