Endoplasmic reticulum stress interferes with the development of type 1 regulating T cells

• Published in: Inflammation research 2024-03, Vol.73 (3), p.381-392
• Main Authors: Feng, Baisui, Liu, Huazhen, Yao, Wenkai, Li, Yan, Wu, Gaohui, Yang, Liteng, Yang, Pingchang
• Format: Article
• Language: English
• Subjects: Allergology; Biomedical and Life Sciences; Biomedicine; CD25 antigen; CD4 antigen; Cell activation; Cell culture; Colitis, Ulcerative - pathology; Deregulation; Dermatology; Endoplasmic reticulum; Gene sequencing; Humans; Immunology; Lymphocytes; Lymphocytes T; Neurology; Nitrophenol; Original Research Paper; p-Nitrophenol; Pathogenesis; Pharmacology/Toxicology; Rheumatology; RING finger proteins; Stress; Synergistic effect; T-Lymphocytes, Regulatory; Ulcerative colitis
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-023-01841-w

Background A variety of stimuli can cause endoplasmic reticulum (ER) stress, which is a common cellular reaction. It is not yet clear how ER stress contributes to the pathogenesis of ulcerative colitis (UC). The deregulation of regulatory T cell (Treg) is associated with UC. The goal of this study is to shed light on how ER stress affects Treg’s development. Methods CD4 + CD25 − T cells were isolated from blood samples collected from UC patients and healthy control (HC) subjects. ER stress-associated molecule expression in CD4 + CD25 − T cell was assessed by RNA sequencing and RT-qPCR. Results The presence of ER stress in peripheral CD4 + CD25 − T cells was observed in patients with UC compared to HC subjects. The induction of ER stress in HC CD4 + CD25 − T cells by polyclonal activation was made worse by the presence of 3-methyl-4-nitrophenol (MNP; a common environmental pollutant). Exposure to MNP in culture resulted in an increase in the expression of ring finger protein 20 (Rnf20) in CD4 + CD25 − T cells. The synergistic effects of MNP and ER stress on the reduction of IL-10 levels in CD4 + CD25 − T cells are mediated by Rnf20, which prevents the development of Tr1 cells. Inhibition of Rnf20 resulted in the development of Tr1 cells from CD4 + CD25 − T cells in UC patients. Conclusions The synergistic effects of ER stress and MNP interfere with the development of Tr1 cells. The development of Tr1 from CD4 + CD25 − T cells in patients with UC is re-established by Rnf20 inhibition.