美国约翰霍普金斯大学医学院Xinzhong Dong和Nathan K. Archer共同合作，近期取得重要工作进展。他们研究发现源自角质细胞的防御素激活中性粒细胞特异性受体Mrgpra2a/b以防止皮肤菌群失调和细菌感染。相关论文2022年7月25日在线发表于《免疫》杂志上。

研究人员发现上皮细胞来源的抗菌肽防御素激活了中性粒细胞上的孤儿G蛋白偶联受体（GPCR）Mrgpra2a/b。该信号轴是有效的中性粒细胞介导的皮肤免疫和微生物群落稳态所必需的。研究人员在角质形成细胞或Mrgpra2a/b中产生了缺乏整个Defensin（Def）基因簇的突变小鼠系。Def和Mrgpra2突变动物都表现出皮肤生态失调，微生物多样性降低和葡萄球菌物种的扩张。

防御素和Mrgpra2对于对抗金黄色葡萄球菌感染和中性粒细胞脓肿的形成至关重要，这是抗菌免疫的标志。防御素对Mrgpra2的激活触发了中性粒细胞释放IL-1β和CXCL2，这对于适当放大和传播抗菌免疫反应至关重要。这项研究证明了通过防御素-Mrgpra2轴的上皮-中性粒细胞信号传导通路，在维持健康的皮肤生态和促进抗菌宿主防御中的重要性。

据介绍，健康的皮肤保持着多样化的微生物群和强大的免疫系统来抵抗感染。

附：英文原文

Title: Keratinocyte-derived defensins activate neutrophil-specific receptors Mrgpra2a/b to prevent skin dysbiosis and bacterial infection

Author: Xintong Dong, Nathachit Limjunyawong, Elizabeth I. Sypek, Gaofeng Wang, Roger V. Ortines, Christine Youn, Martin P. Alphonse, Dustin Dikeman, Yu Wang, Mark Lay, Ruchita Kothari, Chirag Vasavda, Priyanka Pundir, Loyal Goff, Lloyd S. Miller, Wuyuan Lu, Luis A. Garza, Brian S. Kim, Nathan K. Archer, Xinzhong Dong

Issue&Volume: 2022-07-25

Abstract: Healthy skin maintains a diverse microbiome and a potent immune system to fight off infections. Here, we discovered that the epithelial-cell-derived antimicrobial peptides defensins activated orphan G-protein-coupled receptors (GPCRs) Mrgpra2a/b on neutrophils. This signaling axis was required for effective neutrophil-mediated skin immunity and microbiome homeostasis. We generated mutant mouse lines lacking the entire Defensin (Def) gene cluster in keratinocytes or Mrgpra2a/b. Def and Mrgpra2 mutant animals both exhibited skin dysbiosis, with reduced microbial diversity and expansion of Staphylococcus species. Defensins and Mrgpra2 were critical for combating S. aureus infections and the formation of neutrophil abscesses, a hallmark of antibacterial immunity. Activation of Mrgpra2 by defensin triggered neutrophil release of IL-1β and CXCL2 which are vital for proper amplification and propagation of the antibacterial immune response. This study demonstrated the importance of epithelial-neutrophil signaling via the defensin-Mrgpra2 axis in maintaining healthy skin ecology and promoting antibacterial host defense.

DOI: 10.1016/j.immuni.2022.06.021

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00294-1