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Chen, X., Jaiswal, A., & Costliow, Z. (2022). pH sensing controls tissue inflammation by modulating cellular metabolism and endo-lysosomal function of immune cells. Nature Immunology, 23(7), 1063–1075. Added by: Dr. Enrique Feoli (04/07/2025, 18:14) Last edited by: Dr. Enrique Feoli (04/07/2025, 18:15) |
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| Resource type: Journal Article DOI: 10.1038/s41590-022-01231-0 ID no. (ISBN etc.): 1529-2908 BibTeX citation key: Chen2022 View all bibliographic details  |
Categories: BioAcyl Corp, BioAcyl Corp Subcategories: Microecoambiente, Microenvironment Creators: Chen, Costliow, Jaiswal Collection: Nature Immunology |
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| Abstract |
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Extracellular acidification occurs in inflamed tissue and the tumor microenvironment; however, a systematic study on how pH sensing contributes to tissue homeostasis is lacking. Here, we examine cell type-specific roles of the pH sensor GPR65 and its inflammatory disease-associated I231L coding variant in inflammation control. GPR65 I231L knock-in mice are highly susceptible to both bacterial infection-induced and T cell-driven colitis. Mechanistically, GPR65 I231L elicits a cytokine imbalance through impaired Th17 and Th22 differentiation and IL-22 production in association with altered cellular metabolism controlled through the cAMP-CREB-DGAT1 axis. In dendritic cells, GPR65 I231L elevates IL-12 and IL-23 release at acidic pH and alters endo-lysosomal fusion and degradation capacity, resulting in enhanced antigen presentation. This study highlights GPR65 I231L as a multistep risk factor in intestinal inflammation and illuminates a mechanism by which pH sensing controls inflammatory circuits and tissue homeostasis.
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