ER stress modulates the immune regulatory ability in gut M2 cells of patients with ulcerative colitis

This study aims to characterize the impaired immune regulatory function of M4 obtained from UC patient colon lavage fluid (CLF). M4s 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 M4s (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.