CNS myelin induces regulatory functions of DC-SIGN-expressing, antigen-presenting cells via cognate interaction with MOG.
CNS myelin induces regulatory functions of DC-SIGN-expressing, antigen-presenting cells via cognate interaction with MOG.
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CNS 髓磷脂通过与 MOG 的同源相互作用诱导表达 DC-SIGN 的抗原呈递细胞的调节功能。
DOI：
10.1084/jem.20122192
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发表时间：
2014-06-30
期刊：
影响因子：
--
通讯作者：
van Kooyk Y
中科院分区：
文献类型：
--
作者：
García-Vallejo JJ;Ilarregui JM;Kalay H;Chamorro S;Koning N;Unger WW;Ambrosini M;Montserrat V;Fernandes RJ;Bruijns SC;van Weering JR;Paauw NJ;O'Toole T;van Horssen J;van der Valk P;Nazmi K;Bolscher JG;Bajramovic J;Dijkstra CD;'t Hart BA;van Kooyk Y
人髓鞘少突胶质细胞糖蛋白用岩藻糖基化N-聚糖修饰，所述岩藻糖基化N-聚糖被控制免疫稳态的DC-SIGN+ DC和小胶质细胞识别。髓鞘少突胶质细胞糖蛋白（MOG）是中枢神经系统髓鞘的一种成分，是神经炎性疾病多发性硬化（MS）的重要自身抗原。然而，它的功能仍然未知。在这里，我们表明，在健康的人髓鞘，MOG是装饰岩藻糖基化的N-聚糖，支持识别的C型凝集素受体（CDFI）DC特异性细胞间粘附分子-3-抓取非整联蛋白（DC-SIGN）的小胶质细胞和DC。MOG与DC-SIGN在同时TLR 4活化的情况下的相互作用导致以DC-SIGN-、糖基化-和Raf 1-依赖性方式增强IL-10分泌和降低T细胞增殖。少突胶质细胞暴露于促炎因子导致岩藻糖基转移酶表达下调，反映在MS病变部位的糖基化改变。事实上，去除髓磷脂上的岩藻糖降低了DC-SIGN依赖的稳态控制，并导致炎性小体活化，增加了T细胞增殖和向Th 17倾向表型分化。这些数据证明了髓磷脂糖基化在通过MOG-DC-SIGN稳态调节轴控制健康人脑中的免疫稳态中的新作用，所述稳态调节轴由影响糖基化的炎性损伤组成。这一现象应被视为恢复MS免疫耐受的基础。
Human myelin oligodendrocyte glycoprotein is decorated with fucosylated N-glycans that are recognized by DC-SIGN+ DCs and microglia that control immune homeostasis. Myelin oligodendrocyte glycoprotein (MOG), a constituent of central nervous system myelin, is an important autoantigen in the neuroinflammatory disease multiple sclerosis (MS). However, its function remains unknown. Here, we show that, in healthy human myelin, MOG is decorated with fucosylated N-glycans that support recognition by the C-type lectin receptor (CLR) DC-specific intercellular adhesion molecule-3–grabbing nonintegrin (DC-SIGN) on microglia and DCs. The interaction of MOG with DC-SIGN in the context of simultaneous TLR4 activation resulted in enhanced IL-10 secretion and decreased T cell proliferation in a DC-SIGN-, glycosylation-, and Raf1-dependent manner. Exposure of oligodendrocytes to proinflammatory factors resulted in the down-regulation of fucosyltransferase expression, reflected by altered glycosylation at the MS lesion site. Indeed, removal of fucose on myelin reduced DC-SIGN–dependent homeostatic control, and resulted in inflammasome activation, increased T cell proliferation, and differentiation toward a Th17-prone phenotype. These data demonstrate a new role for myelin glycosylation in the control of immune homeostasis in the healthy human brain through the MOG–DC-SIGN homeostatic regulatory axis, which is comprised by inflammatory insults that affect glycosylation. This phenomenon should be considered as a basis to restore immune tolerance in MS.
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影响因子：
3.3
作者：
Fabriek, BO;Zwernmer, JNP;Castelijns, JA
通讯作者：
Castelijns, JA
DOI：
10.1038/nri2569
发表时间：
2009-07
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Geijtenbeek TB;Gringhuis SI
通讯作者：
Gringhuis SI
影响因子：
15.3
作者：
Geijtenbeek, TBH;van Vliet, SJ;Koppel, EA;Sanchez-Hernandez, M;Vandenbroucke-Grauls, CMJE;Appelmelk, B;van Kooyk, Y
通讯作者：
van Kooyk, Y
DOI：
10.1084/jem.194.6.769
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hawiger D;Inaba K;Dorsett Y;Guo M;Mahnke K;Rivera M;Ravetch JV;Steinman RM;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
2.9
作者：
García-Vallejo, JJ;Van het Hof, B;Van Dijk, W
通讯作者：
Van Dijk, W