AUTHOR=Ushio Aya , Arakaki Rieko , Otsuka Kunihiro , Yamada Akiko , Tsunematsu Takaaki , Kudo Yasusei , Aota Keiko , Azuma Masayuki , Ishimaru Naozumi 

TITLE=CCL22-Producing Resident Macrophages Enhance T Cell Response in Sjögren's Syndrome

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.02594

DOI=10.3389/fimmu.2018.02594

ISSN=1664-3224

ABSTRACT=<p>Macrophages (MΦs) are critical regulators of immune response and serve as a link between innate and acquired immunity. The precise mechanism of involvement of tissue-resident MΦs in the pathogenesis of autoimmune diseases is not clear. Here, using a murine model for Sjögren's syndrome (SS), we investigated the role of tissue-resident MΦs in the onset and development of autoimmunity. Two unique populations of CD11b<sup>high</sup> and CD11b<sup>low</sup> resident MΦs were observed in the target tissue of the SS model. Comprehensive gene expression analysis of chemokines revealed effective production of CCL22 by the CD11b<sup>high</sup> MΦs. CCL22 upregulated the migratory activity of CD4<sup>+</sup> T cells by increasing CCR4, a receptor of CCL22, on T cells in the SS model. In addition, CCL22 enhanced IFN-γ production of T cells of the SS model, thereby suggesting that CCL22 may impair the local immune tolerance in the target organ of the SS model. Moreover, administration of anti-CCL22 antibody suppressed autoimmune lesions in the SS model. Finally, histopathological analysis revealed numerous CCL22-producing MΦs in the minor salivary gland tissue specimens of the SS patients. CCL22-producing tissue-resident MΦs may control autoimmune lesions by enhancing T cell response in the SS model. These results suggest that specific chemokines and their receptors may serve as novel therapeutic or diagnostic targets for SS.</p>