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

## TL;DR

Deleting the TMEM268 protein in mice weakens their immune response to infections by reducing CD11b signaling, leading to worse sepsis outcomes.

## Contribution

This study reveals TMEM268's role in regulating CD11b and its impact on anti-infectious immunity in mice.

## Key findings

- Tmem268 deficiency worsens sepsis by increasing bacterial burden and tissue damage.
- TMEM268 prevents CD11b degradation via the endosome–lysosome pathway, enhancing phagocyte function.
- Loss of TMEM268 impairs phagocyte adhesion, migration, and phagocytosis during infection.

## 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.

TMEM268 interacts with the β2 integrin subunit CD11b and attenuates its degradation via the endosome–lysosome pathway, thereby promoting phagocyte adhesion, migration, phagocytosis and bacterial clearance during sepsis.

Tmem268-deficiency impairs bacterial clearance and aggravates CLP-induced sepsis.Tmem268-deficiency suppresses phagocyte adhesion, migration and phagocytosis by downregulating CD11b.Tmem268 knockout promotes CD11b degradation via the endosomal–lysosomal pathway.

Tmem268-deficiency impairs bacterial clearance and aggravates CLP-induced sepsis.

Tmem268-deficiency suppresses phagocyte adhesion, migration and phagocytosis by downregulating CD11b.

Tmem268 knockout promotes CD11b degradation via the endosomal–lysosomal pathway.

TMEM268 interacts with the β2 integrin subunit CD11b and attenuates its degradation via the endosome–lysosome pathway, thereby promoting phagocyte adhesion, migration, phagocytosis and bacterial clearance during sepsis.