McGowan Erin N S, Wong Osanna, Jones Eleanor, Nguyen Julie, Wee Janet, Demaria Maria C, Deliyanti Devy, Johnson Chad J, Hickey Michael J, McConville Malcolm J, Wilkinson-Berka Jennifer L, Wright Mark D, Binger Katrina J
Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3052, Australia.
Department of Immunology and Pathology, Alfred Research Alliance, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia.
iScience. 2022 Jun 3;25(7):104520. doi: 10.1016/j.isci.2022.104520. eCollection 2022 Jul 15.
Phagocytes 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. phagocytes exhibited excessive migration during models of peritoneal inflammation, superfusion of CXCL1, retinopathy of prematurity, and infection with the protozoan parasite . However, with the latter, while macrophages infiltrated infection sites at higher proportions, cutaneous lesions were larger and persisted, indicating a failure to control infection. Analyses of bone-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.
吞噬细胞迁移至组织中以对抗感染并维持组织稳态。由于吞噬细胞迁移和功能失调可导致炎症或易感性感染，因此识别控制这些过程的分子至关重要。在此，我们表明四跨膜蛋白CD82可抑制中性粒细胞和巨噬细胞向组织中的迁移。在腹膜炎症模型、CXCL1灌注、早产儿视网膜病变以及原生动物寄生虫感染期间，吞噬细胞表现出过度迁移。然而，对于后者，虽然巨噬细胞以更高比例浸润感染部位，但皮肤病变更大且持续存在，表明无法控制感染。对骨髓来源巨噬细胞的分析表明，CD82缺陷改变了细胞形态，并损害了抗炎激活反应中的基因表达和代谢。总之，这项工作揭示了CD82在抑制吞噬细胞浸润和介导其对刺激信号的分化方面的重要作用。
