Article ; Online: ATP citrate lyase (ACLY)-dependent immunometabolism in mucosal T cells drives experimental colitis in vivo.
2024 Volume 73, Issue 4, Page(s) 601–612
Abstract: Objective: Mucosal T cells play a major role in inflammatory bowel disease (IBD). However, their immunometabolism during intestinal inflammation is poorly understood. Due to its impact on cellular metabolism and proinflammatory immune cell function, we ... ...
| Abstract | Objective: Mucosal T cells play a major role in inflammatory bowel disease (IBD). However, their immunometabolism during intestinal inflammation is poorly understood. Due to its impact on cellular metabolism and proinflammatory immune cell function, we here focus on the enzyme ATP citrate lyase (ACLY) in mucosal T cell immunometabolism and its relevance for IBD. Design: ACLY expression and its immunometabolic impact on colitogenic T cell function were analysed in mucosal T cells from patients with IBD and in two experimental colitis models. Results: ACLY was markedly expressed in colon tissue under steady-state conditions but was significantly downregulated in lamina propria mononuclear cells in experimental dextran sodium sulfate-induced colitis and in CD4 Conclusion: ACLY controls mucosal T cell immunometabolism and experimental colitis. Therapeutic modulation of ACLY expression in T cells emerges as a novel strategy to promote the resolution of intestinal inflammation. |
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| MeSH term(s) | Humans ; Animals ; Intraepithelial Lymphocytes/metabolism ; ATP Citrate (pro-S)-Lyase/metabolism ; CD8-Positive T-Lymphocytes/metabolism ; Colitis/metabolism ; Inflammatory Bowel Diseases ; Inflammation/metabolism ; Butyrates ; Intestinal Mucosa/metabolism ; Dextran Sulfate ; Disease Models, Animal | |||||
| Chemical Substances | ATP Citrate (pro-S)-Lyase (EC 2.3.3.8) ; Butyrates ; Dextran Sulfate (9042-14-2) | |||||
| Language | English | |||||
| Publishing date | 2024-03-07 | |||||
| Publishing country | England | |||||
| Document type | Journal Article | |||||
| ZDB-ID | 80128-8 | |||||
| ISSN | 1468-3288 ; 0017-5749 | |||||
| ISSN (online) | 1468-3288 | |||||
| ISSN | 0017-5749 | |||||
| DOI | 10.1136/gutjnl-2023-330543 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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