Glycosyltransferase Extl1 promotes CCR7-mediated dendritic cell migration to restrain infection and autoimmunity

被引：6
|
作者：
Liu, Juan [1 ]
Cheng, Yujie [1 ]
Zhang, Xiaomin [1 ]
Chen, Yali [2 ]
Zhu, Ha [1 ]
Chen, Kun [2 ]
Liu, Shuxun [1 ]
Li, Zhiqing [1 ]
Cao, Xuetao [1 ,2 ,3 ]
机构：
[1] Second Mil Med Univ, Inst Immunol, Natl Key Lab Med Immunol, Shanghai 200433, Peoples R China
[2] Chinese Acad Med Sci, Inst Basic Med Sci, Peking Union Med Coll, Dept Immunol,Ctr Immunotherapy, Beijing 100005, Peoples R China
[3] Nankai Univ, Inst Immunol, Coll Life Sci, Frontier Res Ctr Cell Response, Tianjin 300071, Peoples R China
来源：
CELL REPORTS | 2023年 / 42卷 / 01期
基金：
中国国家自然科学基金;
关键词：
HEPARAN-SULFATE; CCR7; TOLERANCE; IMMUNITY; REVEALS; LIGANDS; RELIES;
D O I：
10.1016/j.celrep.2023.111991
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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 demon-strate that the Extl1 (Exostosin like glycosyltransferase 1) promotes CCR7-triggered DC migration in a hep-aran 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.
引用
收藏
页数：25
相关论文
共 26 条
  • [21] TGF-β1-induced EMT promotes targeted migration of breast cancer cells through the lymphatic system by the activation of CCR7/CCL21-mediated chemotaxis
    Pang, M-F
    Georgoudaki, A-M
    Lambut, L.
    Johansson, J.
    Tabor, V.
    Hagikura, K.
    Jin, Y.
    Jansson, M.
    Alexander, J. S.
    Nelson, C. M.
    Jakobsson, L.
    Betsholtz, C.
    Sunds, M.
    Karlsson, M. C. I.
    Fuxe, J.
    ONCOGENE, 2016, 35 (06) : 748 - 760
  • [22] TGF-β1-induced EMT promotes targeted migration of breast cancer cells through the lymphatic system by the activation of CCR7/CCL21-mediated chemotaxis
    M-F Pang
    A-M Georgoudaki
    L Lambut
    J Johansson
    V Tabor
    K Hagikura
    Y Jin
    M Jansson
    J S Alexander
    C M Nelson
    L Jakobsson
    C Betsholtz
    M Sund
    M C I Karlsson
    J Fuxe
    Oncogene, 2016, 35 : 748 - 760
  • [23] Ang-(1-7) promotes the migration and invasion of human renal cell carcinoma cells via Mas-mediated AKT signaling pathway
    Zheng, Shuai
    Yang, Ying
    Song, Ran
    Yang, Xiaomei
    Liu, Hua
    Ma, Qian
    Yang, Longyan
    Meng, Ran
    Tao, Tao
    Wang, Songlin
    He, Junqi
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2015, 460 (02) : 333 - 340
  • [24] Succinate promotes stem cell migration through the GPR91-dependent regulation of DRP1-mediated mitochondrial fission (vol 7, 12582, 2017)
    Ko, So Hee
    Choi, Gee Euhn
    Oh, Ji Young
    Lee, Hyun Jik
    Kim, Jun Sung
    Chae, Chang Woo
    Choi, Diana
    Han, Ho Jae
    SCIENTIFIC REPORTS, 2018, 8
  • [25] Infection of microglia with Porphyromonas gingivalis promotes cell migration and an inflammatory response through the gingipain-mediated activation of protease-activated receptor-2 in mice (vol 7, 2017)
    Liu, Yicong
    Wu, Zhou
    Nakanishi, Yurika
    Ni, Junjun
    Hayashi, Yoshinori
    Takayama, Fumiko
    Zhou, Yanmin
    Kadowaki, Tomoko
    Nakanishi, Hiroshi
    SCIENTIFIC REPORTS, 2018, 8
  • [26] Attenuation of Intestinal Epithelial Cell Migration During Cryptosporidium parvum Infection Involves Parasite Cdg7_FLc_1030 RNA-Mediated Induction and Release of Dickkopf-1
    Ming, Zhenping
    Wang, Yang
    Gong, Ai-Yu
    Zhang, Xin-Tian
    Li, Min
    Chen, Ting
    Mathy, Nicholas W.
    Strauss-Soukup, Juliane K.
    Chen, Xian-Ming
    JOURNAL OF INFECTIOUS DISEASES, 2018, 218 (08): : 1336 - 1347
123