2. Academic Validation
  3. Multiomics analyses reveal a critical role of selenium in controlling T cell differentiation in Crohn's disease

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

  • Immunity. 2021 Aug 10;54(8):1728-1744.e7. doi: 10.1016/j.immuni.2021.07.004.
Ling-Jie Huang 1,  Xin-Tao Mao 2,  Yi-Yuan Li 3,  Dan-Dan Liu 2,  Ke-Qi Fan 2,  Rong-Bei Liu 1,  Ting-Ting Wu 1,  Hao-Li Wang 2,  Yu Zhang 1,  Bing Yang 2,  Cun-Qi Ye 2,  Jiang-Yan Zhong 2,  Ren-Jie Chai 4,  Qian Cao 5,  Jin Jin 6
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, China.
  • 2 MOE Laboratory of Biosystem Homeostasis and Protection and Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
  • 3 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.
  • 4 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.
  • 5 Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, China. Electronic address: caoq@zju.edu.cn.
  • 6 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.
PMID: 34343498 DOI: 10.1016/j.immuni.2021.07.004
Abstract

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.

Keywords

Crohn’s disease; T cell; TRIM21; metabolomics; one-carbon metabolism; selenoprotein W; single-cell RNA sequencing.

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