1. NPSR1 promotes chronic colitis through regulating CD4 + T cell effector function in inflammatory bowel disease.
- Author
-
Peng Y, Chen L, Chen X, Lin J, Wei J, Cheng J, Zhou F, Ge L, Zhou R, Ding F, and Wang X
- Abstract
Background: Neuropeptide S receptor 1 (NPSR1) has been implicated in the the onset of inflammatory bowel disease (IBD), though its exact mechanism remains unclear. This study investigates the role of NPSR1 in regulating CD4
+ T cell effector function in IBD., Methods: Peripheral blood and colonic mucosal biopsies from IBD patients, as well as dextran sodium sulfate (DSS)-induced mouse colitis models, were analyzed to assess the effects of NPSR1 on colitis and CD4+ T cell-mediated immune responses. NPSR1 knockdown was conducted both in vitro and in vivo to elucidate underlying mechanisms. Expression of NPSR1 and CD4+ T cell-related factors was measured using quantitative real-time PCR, immunoblotting, cytometric bead array, immunofluorescence, and immunohistochemistry. CD4 + T cell effector functions were evaluated through flow cytometry, EdU incorporation assay, Annexin V-FITC/PI staining, and transwell assay., Results: NPSR1 expression was elevated in the intestinal tissues from IBD patients. Its downregulation provided protection in DSS-induced mouse colitis models. NPSR1 correlated positively with CD4 + T cell-mediated inflammation, and its knockdown reduced CD4+ T cell-mediated immune responses and inhibited CD4+ T cell differentiation. Additionally, NPSR1 knockdown decreased CD4+ T cell proliferation, increased apoptosis, and enhanced CCL2-induced migration in vitro, while significantly reducing Th1 cell chemotaxis in vivo., Conclusions: This study demonstrates that NPSR1 promotes chronic colitis by regulating CD4 + T cell effector functions in IBD, offering potential new therapeutic strategies for IBD treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)- Published
- 2024
- Full Text
- View/download PDF