Glycosyltransferase Extl1 promotes CCR7-mediated dendritic cell migration to restrain infection and autoimmunity.
Glycosyltransferase Extl1 promotes CCR7-mediated dendritic cell migration to restrain infection and autoimmunity.
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糖基转移酶Extl1促进CCR7介导的树突状细胞迁移以抑制感染和自身免疫
DOI：
10.1016/j.celrep.2023.111991
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发表时间：
2023-01
期刊：
影响因子：
8.8
通讯作者：
Xuetao Cao
中科院分区：
文献类型：
--
作者：
Juan Liu;Yujie Cheng;Xiaomin Zhang;Yali Chen;Ha Zhu;Kun Chen;Shuxun Liu;Zhiqing Li;Xuetao Cao
ccr7触发的DC向引流淋巴结的迁移对于保护性免疫的启动和免疫耐受的维持至关重要。如何促进ccr7介导的DC迁移来决定炎症和稳态条件下T细胞的反应仍然知之甚少。在这里，我们证明了Extl1 （Exostosin like glycosyltransferase 1）以一种依赖硫酸肝素蛋白聚糖（HSPG）的方式促进ccr7触发的DC迁移。从机制上讲，Extl1通过其糖基转移酶结构域介导HSPG的产生，抑制C1q的表达。Extl1/HSPG轴解除了c1q介导的对CCR7表面表达和内化的限制，从而增强了CCR7依赖性迁移信号的激活。因此，在抵抗细菌感染的免疫防御中，dc介导的Th1和Th17应答以及在预防自身免疫的Treg细胞发育中，Extl1是必需的。我们的研究为ccr7触发的DC迁移在免疫和耐受性中的调节提供了机制见解，并为感染性和自身免疫性疾病的治疗提供了潜在的靶点。
CCR7-triggered DC migration toward draining lymph nodes is critical for the initiation of protective immunity and maintenance of immune tolerance. How to promote CCR7-mediated DC migration to determine T cell responses under inflammatory and homeostatic conditions remains poorly understood. Here we demonstrate that the Extl1 (Exostosin like glycosyltransferase 1) promotes CCR7-triggered DC migration in a heparan sulfate proteoglycans (HSPG)-dependent manner. Mechanistically, Extl1 mediates HSPG production via its glycosyltransferase domain to inhibit C1q expression. Extl1/HSPG axis relieves C1q-mediated restriction of CCR7 surface expression and internalization, and thus enhances CCR7-dependent migratory signaling activation. Consequently, Extl1 is required for DC-mediated Th1 and Th17 responses in immune defense against bacterial infection and for Treg cell development in the prevention of autoimmunity. Our study adds mechanistic insights to the regulation of CCR7-triggered DC migration in immunity and tolerance and provides a potential target for the treatment of infectious and autoimmune diseases.
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影响因子：
64.5
作者：
Clausen, Thomas Mandel;Sandoval, Daniel R.;Esko, Jeffrey D.
通讯作者：
Esko, Jeffrey D.
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
8.8
作者：
K. Kamimura;Ai Odajima;Yuko Ikegawa;Chikako Maru;N. Maeda
通讯作者：
K. Kamimura;Ai Odajima;Yuko Ikegawa;Chikako Maru;N. Maeda
影响因子：
64.8
作者：
Briard B;Fontaine T;Samir P;Place DE;Muszkieta L;Malireddi RKS;Karki R;Christgen S;Bomme P;Vogel P;Beau R;Mellado E;Ibrahim-Granet O;Henrissat B;Kalathur RC;Robinson C;Latgé JP;Kanneganti TD
通讯作者：
Kanneganti TD
DOI：
10.1073/pnas.131188498
发表时间：
2001-06-19
影响因子：
11.1
作者：
Kim, BT;Kitagawa, H;Sugahara, K
通讯作者：
Sugahara, K