Department of Pathology, The Sixth People's Hospital of Chengdu, Chengdu 610000, Sichuan Province, China.
Department of Pathology, Affiliated Hospital of Guizhou Medical University, Guiyang 550000, Guizhou Province, China.
Tissue Cell. 2024 Feb;86:102285. doi: 10.1016/j.tice.2023.102285. Epub 2023 Dec 2.
Inflammatory bowel disease (IBD) is one of the most common diseases in the digestive system related to aberrant inflammation. V-set and immunoglobulin domain-containing 4 (VSIG4), a type I transmembrane receptor exclusively expressed in a subset of tissue-resident macrophages, has been reported to exert anti-inflammatory activity in immune-related diseases, which has been not explored in IBD yet. This study aims to explore the role and the potential mechanism of VSIG4 in IBD. Clinical samples were obtained from IBD patients and were examined by immunohistochemical staining. THP-1 cells were differentiated into macrophages, and then stimulated with IL-4 plus IL-13 or LPS to induce pro-inflammatory (M1) or anti-inflammatory (M2) phenotype. Cell transfection was conducted to overexpress VSIG4. Western blot and immunofluorescence assays were performed to assess NLRP3 inflammasome- and pyroptosis-related proteins. Cytokines were measured using ELISA. A cell co-culture model of Caco-2 cells and VSIG4-mediated macrophages were established. Cell viability and apoptosis was examined by CCK-8 and flow cytometry assays, respectively. VSIG4 was downregulated in IBD and was negatively correlated with NLRP3 inflammasome. M1 macrophages exhibited higher levels of NLRP3 inflammasome, pyroptosis and inflammatory response than M2 macrophages, while VSIG4 overexpression efficiently reversed these changes in M1 macrophages. In addition, VSIG4 overexpression partly abolished M1 macrophages-induced cell viability loss, inflammatory response, apoptosis and pyroptosis in Caco-2 cells. Collectively, VSIG4 might alleviate intestinal inflammation through regulating M1/M2 macrophages, providing novel insights for the treatment of human IBD.
炎症性肠病（IBD）是与异常炎症相关的消化系统最常见疾病之一。V -set 和免疫球蛋白结构域包含蛋白 4（VSIG4）是一种仅在特定组织驻留巨噬细胞亚群中表达的 I 型跨膜受体，据报道其在免疫相关疾病中具有抗炎活性，但在 IBD 中尚未得到探索。本研究旨在探讨 VSIG4 在 IBD 中的作用及其潜在机制。本研究从 IBD 患者中获取临床样本，并通过免疫组织化学染色进行检查。将 THP-1 细胞分化为巨噬细胞，然后用 IL-4 加 IL-13 或 LPS 刺激诱导促炎（M1）或抗炎（M2）表型。通过细胞转染过表达 VSIG4。通过 Western blot 和免疫荧光测定评估 NLRP3 炎性体和细胞焦亡相关蛋白。通过 ELISA 测量细胞因子。建立 Caco-2 细胞和 VSIG4 介导的巨噬细胞共培养模型。通过 CCK-8 和流式细胞术分别检测细胞活力和凋亡。VSIG4 在 IBD 中下调，与 NLRP3 炎性体呈负相关。M1 巨噬细胞表现出比 M2 巨噬细胞更高水平的 NLRP3 炎性体、细胞焦亡和炎症反应，而过表达 VSIG4 可有效逆转 M1 巨噬细胞中的这些变化。此外，VSIG4 过表达部分消除了 M1 巨噬细胞诱导的 Caco-2 细胞活力丧失、炎症反应、凋亡和细胞焦亡。总之，VSIG4 可能通过调节 M1/M2 巨噬细胞缓解肠道炎症，为人类 IBD 的治疗提供新的思路。
