Phosphatidylserine receptor Tim-4 is essential for the maintenance of the homeostatic state of resident peritoneal macrophages
Phosphatidylserine receptor Tim-4 is essential for the maintenance of the homeostatic state of resident peritoneal macrophages
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DOI：
10.1073/pnas.0910929107
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发表时间：
2010-05-11
影响因子：
11.1
通讯作者：
Ouyang, Wenjun
中科院分区：
文献类型：
--
作者：
Wong, Kit;Valdez, Patricia A.;Ouyang, Wenjun
Tim-4是在各种巨噬细胞亚群上表达的磷脂酰丝氨酸（PS）受体。介导腹腔巨噬细胞吞噬凋亡细胞。然而，Tim-4在吞噬和免疫应答中的体内功能仍不清楚。在这项研究中，我们表明，蒂姆-4迅速形成点状帽接触凋亡细胞，在吞噬细胞表面上的正常扩散表达。尽管Tim-4在边缘区和易染体巨噬细胞中表达，但Tim-4缺乏仅最小程度地影响几种急性免疫挑战的结果，包括边缘区中凋亡细胞的捕获，易染体巨噬细胞清除凋亡细胞，以及生发中心的形成和针对绵羊红细胞（SRBC）的抗体应答的激发。此外，Tim-4（-/-）驻留的腹膜巨噬细胞（rPM）正常吞噬坏死细胞和其他调理靶点。然而，它们结合和吞噬凋亡细胞的能力在体外和体内均显著受损。最重要的是，Tim-4缺乏导致腹膜中细胞结构增加。静息RPM在培养物中产生更高的TNF-α。相反，它们对LPS的反应受到抑制。我们的数据支持一个不可或缺的作用，蒂姆-4在维持稳态的RPM。
Tim-4 is a phosphatidylserine (PS) receptor that is expressed on various macrophage subsets. It mediates phagocytosis of apoptotic cells by peritoneal macrophages. The in vivo functions of Tim-4 in phagocytosis and immune responses, however, are still unclear. In this study, we show that Tim-4 quickly forms punctate caps on contact with apoptotic cells, in contrast to its normal diffused expression on the surface of phagocytes. Despite its expression in marginal zone and tingible body macrophages, Tim-4 deficiency only minimally affects outcomes of several acute immune challenges, including the trapping of apoptotic cells in the marginal zone, the clearance apoptotic cells by tingible body macrophages, and the formation of germinal centers and elicitation of antibody responses against sheep red blood cells (SRBCs). In addition, Tim-4(-/-) resident peritoneal macrophages (rPMs) phagocytose necrotic cells and other opsonized targets normally. However, their ability to bind and engulf apoptotic cells is significantly compromised both in vitro and in vivo. Most importantly, Tim-4 deficiency results in increased cellularity in the peritoneum. Resting rPMs produce higher TNF-alpha in culture. Their response to LPS, on the contrary, is dampened. Our data support an indispensible role of Tim-4 in maintaining the homeostasis of rPMs.