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

Mengyuan Duan; Xuan Zhang; Yaxin Lou; Jinqiu Feng; Pengli Guo; Shufang Ye; Ping Lv; Yingyu Chen

doi:10.1038/s44319-024-00141-6

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

EMBO Rep. 2024 May 10. doi: 10.1038/s44319-024-00141-6. Online ahead of print.

Authors

Mengyuan Duan¹, Xuan Zhang^{1

2}, Yaxin Lou³, Jinqiu Feng¹, Pengli Guo¹, Shufang Ye¹, Ping Lv¹, Yingyu Chen^{4

5}

Affiliations

¹ Department of Immunology, Peking University School of Basic Medical Sciences; NHC Key Laboratory of Medical Immunology, Peking University, 38 Xueyuan Road, 100191, Beijing, China.
² Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Beijing Pediatric Research Institute, Capital Medical University, National Center for Children's Health, 100045, Beijing, China.
³ Medical and Healthy Analytical Center, Peking University, 38 Xueyuan Road, 100191, Beijing, China.
⁴ Department of Immunology, Peking University School of Basic Medical Sciences; NHC Key Laboratory of Medical Immunology, Peking University, 38 Xueyuan Road, 100191, Beijing, China. yingyu_chen@bjmu.edu.cn.
⁵ Center for Human Disease Genomics, Peking University, 38 Xueyuan Road, 100191, Beijing, China. yingyu_chen@bjmu.edu.cn.

PMID: 38730209
DOI: 10.1038/s44319-024-00141-6

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.

Keywords: CD11b; Integrin; Phagocytes; Sepsis; TMEM268.

Abstract

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