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

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.

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.

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.

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.