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标题：Tetraspanin CD82 restrains phagocyte migration but supports macrophage activation
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作者：Erin N.S. McGowan ; Osanna Wong ; Eleanor Jones 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：7
页码：1-21
DOI：10.1016/j.isci.2022.104520
语种：English
出版社：Elsevier
摘要：SummaryPhagocytes migrate into tissues to combat infection and maintain tissue homeostasis. As dysregulated phagocyte migration and function can lead to inflammation or susceptibility to infection, identifying molecules that control these processes is critical. Here, we show that the tetraspanin CD82 restrains the migration of neutrophils and macrophages into tissues.Cd82−/−phagocytes exhibited excessive migration duringin vivomodels of peritoneal inflammation, superfusion of CXCL1, retinopathy of prematurity, and infection with the protozoan parasiteL. mexicana. However, with the latter, whileCd82−/−macrophages infiltrated infection sites at higher proportions, cutaneousL. mexicanalesions were larger and persisted, indicating a failure to control infection. Analyses ofin vitrobone-marrow-derived macrophages showed CD82 deficiency altered cellular morphology, and impaired gene expression and metabolism in response to anti-inflammatory activation. Altogether, this work reveals an important role for CD82 in restraining phagocyte infiltration and mediating their differentiation in response to stimulatory cues.Graphical abstractDisplay OmittedHighlights•Tetraspanin CD82 restrains phagocyte migration in murine models of inflammation•Excessive migration ofCd82−/−myeloid cells exacerbates retinal inflammation•Cd82−/−macrophages have a reduced ability to clearLeishmania mexicanaparasites•CD82 is required for the normal morphology and activation of M2 macrophagesBiological sciences; Immunology; Immune system