巨噬细胞四聚体MS4A4A能增强dectin-1依赖性的天然杀伤细胞介导的转移抗性，这一成果由意大利罗萨诺研究与保健科学研究所Massimo Locati和Alberto Mantovani团队取得。相关论文于2019年8月发表于国际顶尖学术期刊《自然—免疫学》杂志上。

研究人员报道了MS4A4A只存在于鼠和人类的单核吞噬细胞，并且只在白介素-4或地塞米松的存在的情况下诱导分化。人类的MS4A4A是与正常组织中巨噬细胞亚群中的M2 / M2样分子共表达的，从发炎的滑膜和肿瘤相关巨噬细胞浸润巨噬细胞。MS4A4A在脂质筏上与葡聚糖受体dectin-1产生相互作用。在对dectin-1配体产生响应时，MS4A4A缺陷的巨噬细胞表现出缺陷信号传导和效应分子的缺陷产生。在肿瘤的进展和转移的实验模型中,巨噬细胞的MS4A4A缺陷对原发性肿瘤的生长没有影响,但对于dectin-1介导的激活巨噬细胞和自然杀伤(NK) 细胞介导的转移控制十分重要。因而，MS4A4A 是一种在巨噬细胞分化与极化中选择性表达的四聚体分子， 它对detin-1 依赖的天然杀伤细胞介导的转移抗性激活十分重要。

研究人员表示，质膜四聚体分子MS4A4A在巨噬细胞谱系细胞中选择性地表达，但其功能仍然未知。

附：英文原文

Title: The macrophage tetraspan MS4A4A enhances dectin-1-dependent NK cell–mediated resistance to metastasis

Author: Irene Mattiola, Federica Tomay, Maria De Pizzol, Rita Silva-Gomes, Benedetta Savino, Tamara Gulic, Andrea Doni, Silvia Lonardi, Marie Astrid Boutet, Alessandra Nerviani, Roberta Carriero, Martina Molgora, Matteo Stravalaci, Diego Morone, Irina N. Shalova, Yunquin Lee, Subhra K. Biswas, Giovanna Mantovani, Marina Sironi, Costantino Pitzalis, William Vermi, Barbara Bottazzi, Alberto Mantovani, Massimo Locati

Issue&Volume:Volume 20 Issue 8

Abstract: The plasma membrane tetraspan molecule MS4A4A is selectively expressed by macrophage-lineage cells, but its function is unknown. Here we report that MS4A4A was restricted to murine and human mononuclear phagocytes and was induced during monocyte-to-macrophage differentiation in the presence of interleukin 4 or dexamethasone. Human MS4A4A was co-expressed with M2/M2-like molecules in subsets of normal tissue-resident macrophages, infiltrating macrophages from inflamed synovium and tumor-associated macrophages. MS4A4A interacted and colocalized with the -glucan receptor dectin-1 in lipid rafts. In response to dectin-1 ligands, Ms4a4a-deficient macrophages showed defective signaling and defective production of effector molecules. In experimental models of tumor progression and metastasis, Ms4a4a deficiency in macrophages had no impact on primary tumor growth, but was essential for dectin-1-mediated activation of macrophages and natural killer (NK) cellmediated metastasis control. Thus, MS4A4A is a tetraspan molecule selectively expressed in macrophages during differentiation and polarization, essential for dectin-1-dependent activation of NK cellmediated resistance to metastasis.

DOI: 10.1038/s41590-019-0417-y

Source:https://www.nature.com/articles/s41590-019-0417-y