Authors
Xianting Hu, Zhi Liu, Yao Li, Yannan You, Kaiye Yue, Yuqiong Liang, Chin-San Loo, Jingting Yu, Matthias Leblanc, Dehui Wang, Huabin Li, Ye Zheng
Published in
The Journal of experimental medicine. Volume 223. Issue 2. Feb 02, 2026. Epub Dec 08, 2025.
Abstract
Foxp3+ regulatory T (Treg) cells co-expressing RORγt adopt specialized functions to restrain intestinal inflammation. However, despite extensive characterization, the factors governing RORγt+Foxp3+ Treg specialization remain unclear. Here, we report that transcriptional repressor REV-ERB is critical for the differentiation and function of colonic RORγt+Foxp3+ Treg cells. REV-ERB deficiency exacerbates both TNBS- and oxazolone-induced intestinal inflammation. Mechanistically, REV-ERB promotes RORγt expression through suppressing the expression of transcriptional repressor Bhlhe40, which in turn inhibits c-Maf, a key factor promoting colonic RORγt+Foxp3+ Treg differentiation and function. Moreover, this Bhlhe40-c-Maf axis downstream of REV-ERB also regulates the expression of core colonic Treg signature genes including IL-10 and CTLA-4, while REV-ERB additionally safeguards RORγt+Foxp3+ Treg functional stability by directly suppressing proinflammatory cytokine IL-17A production. Collectively, the present study identifies that REV-ERB along with the downstream Bhlhe40-c-Maf axis jointly controls the RORγt+Foxp3+ Treg differentiation and suppressive function, suggesting that modulating their activities may strengthen RORγt+Foxp3+ Treg function to ameliorate inflammatory bowel diseases.
PMID:
41359309
Bibliographic data and abstract were imported from PubMed on 13 Sep 2026.
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