Abstract
MARCH-I (membrane-associated RING-CH I) has been suggested as a physiological E3 ubiquitin ligase for both MHC class II (MHC II) and B7-2. In this study, we show that MARCH-I-mediated MHC II ubiquitination is necessary for the maintenance of conventional dendritic cell (cDC) functions in the steady state. MARCH-I-deficient cDCs accumulated MHC II and B7-2 and exhibited low Ag-presenting ability for exogenous Ags and low cytokine-producing ability upon stimulation in vivo. Importantly, MHC II, but not B7-2, was required for impaired cDC function induced by loss of MARCH-I in vivo. Moreover, MHC II knockin mice whose MHC II was not ubiquitinated showed dysfunction of cDC similar to that of MARCH-I knockout mice. These results suggest that the accumulation of MHC II resulting from loss of ubiquitination caused cDC abnormality; therefore, MARCH-I may function as a housekeeper of cDC in the steady state.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen Presentation / immunology
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B7-2 Antigen / biosynthesis
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B7-2 Antigen / immunology
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CD4 Antigens / biosynthesis
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CD4 Antigens / immunology
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CD8 Antigens / biosynthesis
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CD8 Antigens / immunology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Flow Cytometry
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Gene Expression
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Gene Expression Regulation / immunology*
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Gene Knock-In Techniques
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Genes, MHC Class II*
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Histocompatibility Antigens Class II / genetics
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Histocompatibility Antigens Class II / immunology*
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Histocompatibility Antigens Class II / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Ubiquitin-Protein Ligases / genetics
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Ubiquitin-Protein Ligases / immunology*
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Ubiquitin-Protein Ligases / metabolism
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Ubiquitination / physiology*
Substances
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B7-2 Antigen
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CD4 Antigens
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CD8 Antigens
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Cd86 protein, mouse
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Histocompatibility Antigens Class II
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MARCH1 protein, mouse
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Ubiquitin-Protein Ligases