Multiomics analyses reveal a critical role of selenium in controlling T cell differentiation in Crohn’s disease.

Aug 5, 2021

Contributor: Ling-Jie Huang,Xin-Tao Mao,Yi-Yuan Li,Dan-Dan Liu,Ke-Qi Fan,Rong-Bei Liu,Ting-Ting Wu,Hao-Li Wang,Yu Zhang,Bing Yang,Cun-Qi Ye,Jiang-Yan Zhong,Ren-Jie Chai,Qian Cao,Jin Jin

Multiomics analyses reveal a critical role of selenium in controlling T cell differentiation in Crohn’s disease.

Inflammatory bowel disease (IBD) mainly includes Crohn’s disease (CD) and ulcerative colitis (UC). Immune disorders play an essential role in the pathogenesis of these two IBDs, but the differences in the immune microenvironment of the colon and their underlying mechanisms remain poorly investigated. Here we examined the immunological features and metabolic microenvironment of untreated individuals with IBD by multiomics analyses. Modulation of CD-specific metabolites, particularly reduced selenium, can obviously shape type 1 T helper (Th1) cell differentiation, which is specifically enriched in CD. Selenium supplementation suppressed the symptoms and onset of CD and Th1 cell differentiation via selenoprotein W (SELW)-mediated cellular reactive oxygen species scavenging. SELW promoted purine salvage pathways and inhibited one-carbon metabolism by recruiting an E3 ubiquitin ligase, tripartite motif-containing protein 21, which controlled the stability of serine hydroxymethyltransferase 2. Our work highlights selenium as an essential regulator of T cell responses and potential therapeutic targets in CD.
Copyright © 2021 Elsevier Inc. All rights reserved.

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About The Expert

Ling-Jie Huang

Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, China.

Xin-Tao Mao

MOE Laboratory of Biosystem Homeostasis and Protection and Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.

Yi-Yuan Li

Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China.

Dan-Dan Liu

MOE Laboratory of Biosystem Homeostasis and Protection and Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.

Ke-Qi Fan

MOE Laboratory of Biosystem Homeostasis and Protection and Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.

Rong-Bei Liu

Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, China.

Ting-Ting Wu

Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, China.

Hao-Li Wang

MOE Laboratory of Biosystem Homeostasis and Protection and Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.

Yu Zhang

Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, China.

Bing Yang

MOE Laboratory of Biosystem Homeostasis and Protection and Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.

Cun-Qi Ye

MOE Laboratory of Biosystem Homeostasis and Protection and Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.

Jiang-Yan Zhong

MOE Laboratory of Biosystem Homeostasis and Protection and Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.

Ren-Jie Chai

Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China; Institute for Stem Cell and Regeneration, Chinese Academy of Science, Beijing 100101, China.

Qian Cao

Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, China. Electronic address: caoq@zju.edu.cn.

Jin Jin

Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, China; MOE Laboratory of Biosystem Homeostasis and Protection and Life Sciences Institute, Zhejiang University, Hangzhou 310058, China. Electronic address: jjin4@zju.edu.cn.

References

PubMed