Cutting edge: requirement of MARCH-I-mediated MHC II ubiquitination for the maintenance of conventional dendritic cells.
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.
Ohmura-Hoshino
Mari
M
Laboratory for Infectious Immunity, RIKENResearch Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa, Japan.
Matsuki
Yohei
Y
Mito-Yoshida
Mari
M
Goto
Eiji
E
Aoki-Kawasumi
Masami
M
Nakayama
Manabu
M
Ohara
Osamu
O
Ishido
Satoshi
S
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000276:immunology; D015704:CD4 Antigens / Q000096:biosynthesis / Q000276:immunology; D016827:CD8 Antigens / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology*; D055879:Gene Knock-In Techniques; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology*
D051940:B7-2 Antigen; D015704:CD4 Antigens; D016827:CD8 Antigens; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; C545340:MARCH1 protein, mouse; D044767:Ubiquitin-Protein Ligases