title: Inflammation-induced CD69+Kupffer cell feedback inhibits T cell proliferation via membrane-bound TGF-β1.
abstract: Kupffer cells, tissue-resident macrophage lineage cell, are enriched in vertebrate liver. The mouse F4/80+Kupffer cells have been subclassified into two subpopulations according to their phenotype and function: CD68+subpopulation with potent reactive oxygen species (ROS) production and phagocytic capacities, and CD11b+subpopulation with a potent capacity to produce T helper 1 cytokines. In addition, CD11b+Kupffer cells/macrophages may be migrated from the bone marrow or spleen, especially in inflammatory conditions of the liver. For analyzing diverse Kupffer cell subsets, we infected mice with Listeria monocytogenes and analyzed the phenotype variations of hepatic Kupffer cells. During L. monocytogenes infection, hepatic CD69+Kupffer cells were significantly induced and expanded, and CD69+Kupffer cells expressed higher level of CD11b, and particularly high level of membrane-bound TGF-β1 (mTGF-β1) but lower level of F4/80. We also found that clodronate liposome administration did not eliminate hepatic CD69+Kupffer cell subset. We consider the hepatic CD69+Kupffer cell population corresponds to CD11b+Kupffer cells, the bone marrow-derived population. Hepatic CD69+Kupffer cells suppressed Ag-nonspecific and OVA-specific CD4 T cell proliferation through mTGF-β1 both in vitro and in vivo, meanwhile, they did not interfere with activation of CD4 T cells. Thus, we have identified a new subset of inflammation-induced CD69+Kupffer cells which can feedback inhibit CD4 T cell response via cell surface TGF-β1 at the late stage of immune response against infection. CD69+Kupffer cells may contribute to protect host from pathological injure by preventing overactivation of immune response.
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gu
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, 200433, China.|National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100730, China.
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, 200433, China. hanyanmei@immunol.org.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Han
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D025461:Feedback, Physiological; D005434:Flow Cytometry; D016130:Immunophenotyping; D007249:Inflammation / Q000378:metabolism*; D007728:Kupffer Cells / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000502:physiology; D008088:Listeriosis / Q000378:metabolism / Q000382:microbiology; D008099:Liver / Q000378:metabolism / Q000382:microbiology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D039481:CD11b Antigen; D016207:Cytokines; D037181:Lectins, C-Type; D010047:Ovalbumin; D053773:Transforming Growth Factor beta1; D000099192:CD69 Antigens
keywords: CD69; Kupffer cell; Listeria monocytogenes; TGF-β1; immune regulation