National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China.
Department of Gastroenterology, XinQiao Hospital, Third Military Medical University, Chongqing, China.
Sci Adv. 2019 Apr 3;5(4):eaau6547. doi: 10.1126/sciadv.aau6547. eCollection 2019 Apr.
The interaction between gastric epithelium and immune response plays key roles in -associated pathology. We demonstrated a procolonization and proinflammation role of MMP-10 in infection. MMP-10 is elevated in gastric mucosa and is produced by gastric epithelial cells synergistically induced by and IL-22 via the ERK pathway. Human gastric MMP-10 was correlated with colonization and the severity of gastritis, and mouse MMP-10 from non-BM-derived cells promoted bacteria colonization and inflammation. colonization and inflammation were attenuated in IL-22, MMP-10, and IL-22MMP-10 mice. MMP-10-associated inflammation is characterized by the influx of CD8 T cells, whose migration is induced via MMP-10-CXCL16 axis by gastric epithelial cells. Under the influence of MMP-10, Reg3a, E-cadherin, and zonula occludens-1 proteins decrease, resulting in impaired host defense and increased colonization. Our results suggest that MMP-10 facilitates persistence and promotes gastritis.
胃上皮细胞与免疫反应的相互作用在幽门螺杆菌相关病理学中起着关键作用。我们证明了 MMP-10 在幽门螺杆菌感染中具有促定植和促炎作用。MMP-10 在胃黏膜中升高，并且通过 ERK 途径由幽门螺杆菌和 IL-22 协同诱导的胃上皮细胞产生。人胃 MMP-10 与幽门螺杆菌定植和胃炎严重程度相关，并且来自非 BM 衍生细胞的小鼠 MMP-10 促进细菌定植和炎症。IL-22、MMP-10 和 IL-22MMP-10 小鼠的幽门螺杆菌定植和炎症减轻。MMP-10 相关炎症的特征是 CD8 T 细胞的浸润，其通过胃上皮细胞的 MMP-10-CXCL16 轴诱导迁移。在 MMP-10 的影响下，Reg3a、E-钙粘蛋白和闭合蛋白-1 蛋白减少，导致宿主防御受损和幽门螺杆菌定植增加。我们的结果表明，MMP-10 促进幽门螺杆菌的持续存在并促进胃炎。
