iScience (Apr 2023)
ER stress modulates the immune regulatory ability in gut M2 cells of patients with ulcerative colitis
Abstract
Summary: This study aims to characterize the impaired immune regulatory function of Mφ obtained from UC patient colon lavage fluid (CLF). Mφs were the largest proportion (21.3 4.0%) of the CLF-derived cellular components. Less abundant and weaker immune suppressive function were observed in M2 Mφs (M2 cells) of the ulcerative colitis (UC) group. High levels of endoplasmic reticulum (ER) stress associated molecules were detected in UC M2 cells. The spliced X box binding protein-1 (XBP1) gene was negatively correlated with programmed death ligand-1 (PD-L1) in UC M2 cells. XBP1 promoted the expression of ring-finger protein 20 (Rnf20) in M2 cells. Rnf20 reduced PD-L1 abundance in UC M2 cells and impaired the immune suppressive ability. Inhibition of Rnf20 restored the immune regulating capacity of M2 cells and suppressed experimental colitis.