title: Phosphatidylserine receptor Tim-4 is essential for the maintenance of the homeostatic state of resident peritoneal macrophages.
abstract: 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.
authors.affiliation: Department of Immunology, Genentech, Inc., South San Francisco, CA 94080, USA.
authors.forename: Kit
authors.initials: K
authors.lastname: Wong
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Valdez
authors.forename: Christine
authors.initials: C
authors.lastname: Tan
authors.forename: Sherry
authors.initials: S
authors.lastname: Yeh
authors.forename: Jo-Anne
authors.initials: JA
authors.lastname: Hongo
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ouyang
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D002448:Cell Adhesion; D002452:Cell Count; D002460:Cell Line; D004912:Erythrocytes / Q000276:immunology; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology*; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D010587:Phagocytosis / Q000276:immunology; D021381:Protein Transport; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011951:Receptors, Complement / Q000276:immunology; D012756:Sheep; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000906:Antibodies; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D011951:Receptors, Complement; C500399:TIM-4 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C408123:phosphatidylserine receptor