title: Interleukin 10 (IL-10)-mediated Immunosuppression: MARCH-I INDUCTION REGULATES ANTIGEN PRESENTATION BY MACROPHAGES BUT NOT DENDRITIC CELLS.
abstract: Efficient immune responses require regulated antigen presentation to CD4 T cells. IL-10 inhibits the ability of dendritic cells (DCs) and macrophages to stimulate antigen-specific CD4 T cells; however, the mechanisms by which IL-10 suppresses antigen presentation remain poorly understood. We now report that IL-10 stimulates expression of the E3 ubiquitin ligase March-I in activated macrophages, thereby down-regulating MHC-II, CD86, and antigen presentation to CD4 T cells. By contrast, IL-10 does not stimulate March-I expression in DCs, does not suppress MHC-II or CD86 expression on either resting or activated DCs, and does not affect antigen presentation by activated DCs. IL-10 does, however, inhibit the process of DC activation itself, thereby reducing the efficiency of antigen presentation in a March-I-independent manner. Thus, IL-10 suppression of antigen presenting cell function in macrophages is March-I-dependent, whereas in DCs, suppression is March- I-independent.
authors.affiliation: Experimental Immunology Branch, NCI, National Institutes of Health, Bethesda, Maryland 20892 and.
authors.forename: Sharad K
authors.initials: SK
authors.lastname: Mittal
authors.affiliation: Experimental Immunology Branch, NCI, National Institutes of Health, Bethesda, Maryland 20892 and.
authors.forename: Kyung-Jin
authors.initials: KJ
authors.lastname: Cho
authors.affiliation: Laboratory of Integrative Infection Immunity, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishido
authors.affiliation: Experimental Immunology Branch, NCI, National Institutes of Health, Bethesda, Maryland 20892 and. Electronic address: paul.roche@nih.gov.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Roche
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D051940:B7-2 Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D015536:Down-Regulation; D004790:Enzyme Induction / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007108:Immune Tolerance / Q000502:physiology*; D016753:Interleukin-10 / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000201:enzymology* / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics
chemical_list: D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; C556062:IL10 protein, mouse; D008070:Lipopolysaccharides; D010446:Peptide Fragments; C438947:ovalbumin (325-339); D016753:Interleukin-10; D010047:Ovalbumin; C545340:MARCH1 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: antigen presentation; dendritic cell; immunosuppression; interleukin; macrophage; major histocompatibility complex (MHC); ubiquitin ligase