Details

Autor(en) / Beteiligte

• Huang, Ling-jie
• Mao, Xin-tao
• Li, Yi-yuan
• Liu, Dan-dan
• Fan, Ke-qi
• Liu, Rong-bei
• Wu, Ting-ting
• Wang, Hao-li
• Zhang, Yu
• Yang, Bing
• Ye, Cun-qi
• Zhong, Jiang-yan
• Chai, Ren-jie
• Cao, Qian
• Jin, Jin

Titel

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

Ist Teil von

• Immunity (Cambridge, Mass.), 2021-08, Vol.54 (8), p.1728-1744.e7

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. [Display omitted] •Th1-like subpopulation and reduced selenium are identified in Crohn’s disease•Selenium suppresses Th1 differentiation in vitro and in vivo•Selenium-induced selenoprotein W inhibits Th1 polarization•Selenoprotein W regulates cellular ROS by altering the balance of purine synthesis Immune disorders play an essential role in the onset of Crohn’s disease and ulcerative colitis, but the differences and underlying mechanisms between these two IBDs remain unclear. Huang et al. identify disease-specific features by multiomics analyses and highlight selenium as having a critical role in T cell responses in Crohn’s disease.