Cutting edge: requirement of MARCH-I-mediated MHC II ubiquitination for the maintenance of conventional dendritic cells

The Journal of Immunology : Official Journal of the American Association of Immunologists
Mari Ohmura-HoshinoSatoshi Ishido

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.

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Citations

Nov 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Even WalsengPaul A Roche
Nov 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Kazuyuki FurutaPaul A Roche
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Mar 10, 2010·Molecules and Cells·Satoshi IshidoMari Ohmura-Hoshino
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