NPSR1 promotes chronic colitis through regulating CD4⁺ T cell effector function in inflammatory bowel disease

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.

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.

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.

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.