Deletion of Tmem268 in mice suppresses anti-infectious immune responses by downregulating CD11b signaling

Abstract

AbstractTransmembrane 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.