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

Baisui Feng; Lingzhi Xu; Shuo Song; Huazhen Liu; Yan Li; Suqin Hu; Qing Shu; Jiangqi Liu; Zhiqiang Liu; Haiqiong Yu; Pingchang Yang

doi:10.1016/j.isci.2023.106498

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

iScience. 2023 Mar 24;26(4):106498. doi: 10.1016/j.isci.2023.106498. eCollection 2023 Apr 21.

Authors

Baisui Feng¹, Lingzhi Xu², Shuo Song^{3

4}, Huazhen Liu^{3

4}, Yan Li¹, Suqin Hu^{3

4}, Qing Shu⁵, Jiangqi Liu⁶, Zhiqiang Liu⁶, Haiqiong Yu⁷, Pingchang Yang^{3

4}

Affiliations

¹ Department of Gastroenterology, Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Department of Immunology, School of Basic Medical Sciences, Weifang Medical University, Weifang, China.
³ Guangdong Provincial Regional Disease Key Laboratory, Shenzhen, China.
⁴ Institute of Allergy & Immunology of Shenzhen University, State Key Laboratory of Respiratory Diseases Division at Shenzhen University, Shenzhen, China.
⁵ Department of Gastroenterology, Shenzhen Second People's Hospital, Shenzhen, China.
⁶ Department of Allergy, Longgang ENT Hospital, Shenzhen, China.
⁷ Department of Pulmonary and Critical Care Medicine, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen518033, China.

Abstract

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.

Keywords: Gastroenterology; Immunology; Transcriptomics; immune response.