MARCH1 protects the lipid raft and tetraspanin web from MHCII proteotoxicity in dendritic cells.
MARCH1 protects the lipid raft and tetraspanin web from MHCII proteotoxicity in dendritic cells.
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DOI：
10.1083/jcb.201611141
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发表时间：
2018-04-02
期刊：
影响因子：
--
通讯作者：
Shin JS
中科院分区：
文献类型：
--
作者：
Oh J;Perry JSA;Pua H;Irgens-Möller N;Ishido S;Hsieh CS;Shin JS
MHCII是树突状细胞作为抗原呈递细胞发挥功能所必需的;然而，抑制MHCII降解通过未知机制损害调节性T细胞的产生。Oh等人现在报道MHCII周转是维持Treg细胞分化所需的脂筏和四跨膜蛋白结构域的稳态的重要质量控制机制。树突状细胞（DC）产生大量的主要组织相容性复合物II（MHCII），作为专职抗原呈递细胞发挥功能。特异性地，DC也以组成型方式泛素化和降解MHCII。缺乏MHCII-泛素化酶膜锚定RING-CH 1或MHCII的泛素受体赖氨酸的小鼠表现出调节性T细胞（Treg）数量的大幅减少，但其潜在机制尚不清楚。在这里，我们报告说，泛素依赖的MHCII营业额是至关重要的，以维持稳态的脂筏和四跨膜蛋白网络在DC。MHCII泛素化的缺乏导致过量的MHCII在质膜中的积累，并且由此产生的对脂筏和四跨膜蛋白网的破坏导致DC接合和激活胸腺细胞以用于Treg细胞分化的能力的显著损害。因此，泛素依赖性MHCII周转代表了一种新的质量控制机制，通过该机制DC维持支持DC的Treg细胞选择功能的膜结构域的稳态。
MHCII is essential for dendritic cells to function as antigen presenting cells; however, inhibiting MHCII degradation impairs regulatory T cell generation by an unknown mechanism. Oh et al. now report that MHCII turnover is an important quality-control mechanism in maintaining homeostasis of the lipid raft and tetraspanin domains required for Treg cell differentiation. Dendritic cells (DCs) produce major histocompatibility complex II (MHCII) in large amounts to function as professional antigen presenting cells. Paradoxically, DCs also ubiquitinate and degrade MHCII in a constitutive manner. Mice deficient in the MHCII-ubiquitinating enzyme membrane-anchored RING-CH1, or the ubiquitin-acceptor lysine of MHCII, exhibit a substantial reduction in the number of regulatory T (Treg) cells, but the underlying mechanism was unclear. Here we report that ubiquitin-dependent MHCII turnover is critical to maintain homeostasis of lipid rafts and the tetraspanin web in DCs. Lack of MHCII ubiquitination results in the accumulation of excessive quantities of MHCII in the plasma membrane, and the resulting disruption to lipid rafts and the tetraspanin web leads to significant impairment in the ability of DCs to engage and activate thymocytes for Treg cell differentiation. Thus, ubiquitin-dependent MHCII turnover represents a novel quality-control mechanism by which DCs maintain homeostasis of membrane domains that support DC’s Treg cell–selecting function.
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影响因子：
30.5
作者：
Anderson, HA;Hiltbold, EM;Roche, PA
通讯作者：
Roche, PA
影响因子：
4.8
作者：
Corcoran, Kathleen;Jabbour, Maurice;Lybarger, Lonnie
通讯作者：
Lybarger, Lonnie
DOI：
10.4049/jimmunol.1101643
发表时间：
2011-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Baravalle G;Park H;McSweeney M;Ohmura-Hoshino M;Matsuki Y;Ishido S;Shin JS
通讯作者：
Shin JS
影响因子：
14.9
作者：
Giudicelli, Veronique;Duroux, Patrice;Ginestoux, Chantal;Folch, Geraldine;Jabado-Michaloud, Joumana;Chaume, Denys;Lefranc, Marie-Paule
通讯作者：
Lefranc, Marie-Paule
供体型CD4（+）CD25（+）调节性T细胞在同种异体骨髓移植后抑制致命的急性移植物抗宿主疾病。
影响因子：
15.3
作者：
Hoffmann, Petra;Ermann, Joerg;Edinger, Matthias;Fathman, C Garrison;Strober, Samuel
通讯作者：
Strober, Samuel