arginase-1–expressing macrophages suppress th2 cytokine–driven inflammation and fibrosisarginase-1-expressing巨噬细胞抑制th2 cytokine-driven炎症和纤维化.pdfVIP

Arginase-1–Expressing Macrophages Suppress Th2 Cytokine–Driven Inflammation and Fibrosis 1. 1. 1 1 John T. Pesce , Thirumalai R. Ramalingam , Margaret M. Mentink-Kane , Mark S. Wilson , Karim C. El 2¤ 2 1 3 2 Kasmi , Amber M. Smith , Robert W. Thompson , Allen W. Cheever , Peter J. Murray *, Thomas A. Wynn1* 1 Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America, 2 Departments of Infectious Diseases and Immunology, St. Jude Children’s Research Hospital, Memphis, Tennessee, United States of America, 3 Biomedical Research Institute, Rockville, Maryland, United States of America Abstract Macrophage-specific expression of Arginase-1 is commonly believed to promote inflammation, fibrosis, and wound healing by enhancing L-proline, polyamine, and Th2 cytokine production. Here, however, we show that macrophage-specific Arg1 functions as an inhibitor of inflammation and fibrosis following infection with the Th2-inducing pathogen Schistosoma mansoni. Although susceptibility to infection was not affected by the conditional deletion of Arg1 in macrophages, Arg1 2/flox;LysMcre mice died at an accelerated rate. The mortality was not due to acute Th1/NOS2-mediated hepatotoxicity or endotoxemia. Instead, granulomatous inflammation, liver fibrosis, and portal hypertension increased in infected 2/flox flox/flox Arg1