2. Academic Validation
  3. Deficiency of immunoglobulin IgSF6 enhances antibacterial effects by promoting ER stress and the inflammatory response in intestinal macrophages

Deficiency of immunoglobulin IgSF6 enhances antibacterial effects by promoting ER stress and the inflammatory response in intestinal macrophages

  • Mucosal Immunol. 2024 Feb 20:S1933-0219(24)00015-1. doi: 10.1016/j.mucimm.2024.02.006.
Yuting Wu 1,  Panrui Zhang 2,  Tianlu Shi 1,  Dan Cao 3,  Wen Pan 4
Affiliations

Affiliations

  • 1 Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, P.R. China.
  • 2 Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China.
  • 3 Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China. Electronic address: [email protected].
  • 4 Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China. Electronic address: [email protected].
PMID: 38387824 DOI: 10.1016/j.mucimm.2024.02.006
Abstract

Immunoglobulin superfamily (IgSF) members are known for their role as glycoproteins expressed on the surface of immune cells, enabling protein-protein interactions to sense external signals during immune responses. However, the functions of immunoglobulins localized within subcellular compartments have been less explored. In this study, we identified an ER-localized immunoglobulin, IgSF member 6 (IgSF6), regulates ER stress and the inflammatory response in intestinal macrophages. Igsf6 expression is sustained by microbiota and significantly upregulated upon Bacterial infection. Mice lacking Igsf6 displayed resistance to S. Tyr challenge but increased susceptibility to dextran sulfate sodium (DSS)-induced colitis. Mechanistically, deficiency of Igsf6 enhanced IRE1α/XBP1s pathway, inflammatory response and ROS production, leading to an increased bactericidal activity of intestinal macrophages. Inhibition of ROS or IRE1α-XBP1 pathway reduced the advantage of Igsf6 deficiency in bactericidal capacity. Together, our findings provide insight into a role for IgSF6 in intestinal macrophages that modulates the ER stress response and maintains intestinal homeostasis.

Keywords

Bactericidal effect; ER stress; IgSF member 6 (IgSF6); Inflammatory disease; Macrophage.

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