PDF(Pubmed)
Abstract：
Transmembrane protein 268 (TMEM268) is a novel, tumor growth-related protein first reported by our laboratory. It interacts with the integrin subunit β4 (ITGB4) and plays a positive role in the regulation of the ITGB4/PLEC signaling pathway. Here, we investigated the effects and mechanism of TMEM268 in anti-infectious immune response in mice. Tmem268 knockout in mice aggravated cecal ligation and puncture-induced sepsis, as evidenced by higher bacterial burden in various tissues and organs, congestion, and apoptosis. Moreover, Tmem268 deficiency in mice inhibited phagocyte adhesion and migration, thus decreasing phagocyte infiltration at the site of infection and complement-dependent phagocytosis. Further findings indicated that TMEM268 interacts with CD11b and inhibits its degradation via the endosome-lysosome pathway. Our results reveal a positive regulatory role of TMEM268 in β2 integrin-associated anti-infectious immune responses and signify the potential value of targeting the TMEM268-CD11b signaling axis for the maintenance of immune homeostasis and immunotherapy for sepsis and related immune disorders.
摘要：
跨膜蛋白268(TMEM268)是一种新型的,我们实验室首次报道的肿瘤生长相关蛋白。它与整合素亚基β4（ITGB4）相互作用，并在ITGB4/PLEC信号通路的调节中起积极作用。这里,我们研究了TMEM268在小鼠抗感染免疫反应中的作用和机制。小鼠的Tmem268基因敲除加重了盲肠结扎和穿孔引起的脓毒症，各种组织和器官的细菌负荷较高，拥塞，和凋亡。此外，小鼠Tmem268缺乏抑制吞噬细胞粘附和迁移，从而减少感染部位的吞噬细胞浸润和补体依赖性吞噬作用。进一步的发现表明TMEM268与CD11b相互作用并通过内体-溶酶体途径抑制其降解。我们的结果揭示了TMEM268在β2整合素相关的抗感染免疫反应中的积极调节作用，并表明靶向TMEM268-CD11b信号轴对于维持免疫稳态和免疫治疗脓毒症和相关免疫疾病的潜在价值。
