Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China; Hubei Provincial Clinical Research Center for Intestinal and Colorectal Diseases, Hubei Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, China.
Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi, China.
Int Immunopharmacol. 2024 Dec 5;142(Pt B):113252. doi: 10.1016/j.intimp.2024.113252. Epub 2024 Sep 26.
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.
神经肽 S 受体 1（NPSR1）已被牵涉到炎症性肠病（IBD）的发病机制中，尽管其确切机制尚不清楚。本研究旨在探讨 NPSR1 在调节 IBD 中 CD4 T 细胞效应功能中的作用。
分析 IBD 患者的外周血和结肠黏膜活检组织，以及葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎模型，以评估 NPSR1 对结肠炎和 CD4 T 细胞介导的免疫反应的影响。通过体外和体内实验进行 NPSR1 敲低，以阐明潜在的机制。使用定量实时 PCR、免疫印迹、细胞因子 bead 阵列、免疫荧光和免疫组织化学来测量 NPSR1 和 CD4 T 细胞相关因子的表达。通过流式细胞术、EdU 掺入测定、Annexin V-FITC/PI 染色和 Transwell 测定评估 CD4+T 细胞效应功能。
NPSR1 在 IBD 患者的肠道组织中表达上调。其下调在 DSS 诱导的小鼠结肠炎模型中提供了保护作用。NPSR1 与 CD4+T 细胞介导的炎症呈正相关，其敲低可降低 CD4 T 细胞介导的免疫反应并抑制 CD4 T 细胞分化。此外，NPSR1 敲低可减少 CD4 T 细胞增殖，增加细胞凋亡，并增强体外 CCL2 诱导的迁移，而体内则可显著减少 Th1 细胞趋化性。
本研究表明，NPSR1 通过调节 IBD 中 CD4+T 细胞效应功能促进慢性结肠炎，为 IBD 治疗提供了潜在的新治疗策略。
