2. Academic Validation
  3. Butyrate ameliorates ulcerative colitis through targeting STING-dependent ER stress signaling and limiting CD4+ TRM T cells accumulation

Butyrate ameliorates ulcerative colitis through targeting STING-dependent ER stress signaling and limiting CD4+ TRM T cells accumulation

  • J Inflamm (Lond). 2025 Nov 24;22(1):50. doi: 10.1186/s12950-025-00475-5.
Tengfei Xiao # 1 2,  Jingjing Kang # 3,  Chuanxiang Zhao 4,  Rong Zhu 1 2,  Mingzhong Sun 5 6,  Yungang Wang 7 8
Affiliations

Affiliations

  • 1 Department of Clinical Laboratory, Yancheng Third People's Hospital, Affiliated Hospital 6 of Nantong University, Yancheng, Jiangsu, 224000, China.
  • 2 Department of Clinical Laboratory, Yancheng Third People's Hospital, The Affiliated Hospital of Jiangsu Vocational College of Medicine, Yancheng, Jiangsu, 224000, China.
  • 3 Department of Clinical Laboratory, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, The First People's Hospital of Yancheng, Yancheng, Jiangsu, 224000, China.
  • 4 Laboratory Medicine, Institute of Medical Genetics and Reproductive Immunity, School of Medical Science, Jiangsu College of Nursing, Huai'an, Jiangsu, 223001, China.
  • 5 Department of Clinical Laboratory, Yancheng Third People's Hospital, Affiliated Hospital 6 of Nantong University, Yancheng, Jiangsu, 224000, China. [email protected].
  • 6 Department of Clinical Laboratory, Yancheng Third People's Hospital, The Affiliated Hospital of Jiangsu Vocational College of Medicine, Yancheng, Jiangsu, 224000, China. [email protected].
  • 7 Department of Clinical Laboratory, Yancheng Third People's Hospital, Affiliated Hospital 6 of Nantong University, Yancheng, Jiangsu, 224000, China. [email protected].
  • 8 Department of Clinical Laboratory, Yancheng Third People's Hospital, The Affiliated Hospital of Jiangsu Vocational College of Medicine, Yancheng, Jiangsu, 224000, China. [email protected].
  • # Contributed equally.
PMID: 41286853 DOI: 10.1186/s12950-025-00475-5
Abstract

This study aimed to investigate the role of butyrate in regulating STING-induced endoplasmic reticulum stress (ERS) and CD4+ tissue-resident memory (TRM) T cells responses during the progression of ulcerative colitis (UC). Our results demonstrated that butyrate significantly alleviated dextran sulfate sodium (DSS)-induced colitis, as evidenced by restored intestinal epithelial architecture, reduced inflammatory cytokine, and decreased CD4+ TRM T cells. These protective effects were likely mediated through modulation of the STING-ERS pathway. Using a CT26 cell model, we further confirmed that STING activation promotes ERS, leading to enhanced secretion of inflammatory factors and subsequent induction of CD4+ TRM T cells. Importantly, butyrate effectively suppressed this STING-initiated inflammatory cascade in intestinal epithelial cells (IECs). Our findings revealed a novel mechanism by which butyrate ameliorates UC through inhibition of the STING-ERS axis in IECs, highlighting its therapeutic potential for UC treatment.

Keywords

Butyrate; CD4+TRM T cells; ERS; Ulcerative colitis; cGSA-STING pathway.

Figures
Products