ケモカイン活性とスカベンジャー受容体活性を有するＳＲ‐ＰＳＯＸ／ＣＸＣＬ１６の自然免疫と獲得免疫における役割解析

Abstract

SR-PSOX and CXCL16, which were originally identified as a scavenger receptor and a transmembrane-type chemokine, respectively, are strikingly proved to be essentially identical. Here, we demonstrate that, while soluble SR-PSOX/CXCL16 is chemotactic for CXCR6-expressing cells, membrane-bound SR-PSOX/CXCL16 mediates adhesion and phagocytosis of both Gram-negative and Gram-positive bacteria. Importantly, our prepared anti- SR/PSOX monoclonal antibody, which suppressed chemotactic activity of SR-PSOX, significantly inhibited bacterial phagocytosis by antigen-presenting cells including dendritic cells. Various scavenger receptor ligands inhibited not only scavenger receptor activity but also chemotactic activities of SR-PSOX. In addition, both activities were similarly impaired in a series of mutants in which one basic amino acid in the chemokine domain of SRPSOX was replaced by alanine. Thus, SR-PSOX/CXCL16 was shown to play a role in both innate and adaptive immunity by mediating phagocytosis of bacteria as well as recruitment of CXCR6-expressing T cells by antigenpresenting cells through the same chemokine domain.