Cutting Edge: Requirement of MARCH-I-Mediated MHC II Ubiquitination for the Maintenance of Conventional Dendritic Cells
Cutting Edge: Requirement of MARCH-I-Mediated MHC II Ubiquitination for the Maintenance of Conventional Dendritic Cells
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DOI：
10.4049/jimmunol.0902178
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发表时间：
2009-12-01
影响因子：
4.4
通讯作者：
Ishido, Satoshi
中科院分区：
文献类型：
--
作者：
Ohmura-Hoshino, Mari;Matsuki, Yohei;Ishido, Satoshi
MARCH-I（膜相关RING-CH I）已被认为是MHC II类（MHC II）和B7-2的生理性E3泛素连接酶。在这项研究中，我们表明，MARCH-I介导的MHC II泛素化是必要的，维持传统的树突状细胞（cDC）的功能在稳定状态。MARCH-I缺陷型cDC积累MHC II和B7-2，并在体内刺激后表现出对外源性Ags的低Ag提呈能力和低细胞因子产生能力。重要的是，MHC II，而不是B7-2，是由体内MARCH-I缺失诱导的cDC功能受损所必需的。此外，MHC II未被泛素化的MHC II敲入小鼠表现出与MARCH-1敲除小鼠相似的cDC功能障碍。这些结果表明，由于泛素化的丧失导致的MHC II的积累导致cDC异常;因此，MARCH-I可能在稳态下作为cDC的管家。免疫学杂志，2009，183：6893-6897.
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. The Journal of Immunology, 2009, 183: 6893-6897.