Extracellular vesicle fibrinogen induces encephalitogenic CD8+T cells in a mouse model of multiple sclerosis

被引：43

作者：

Willis, Cory M. ^{[1
]}

Nicaise, Alexandra M. ^{[1
]}

Menoret, Antoine ^{[2
,3
]}

Ryu, Jae Kyu ^{[4
]}

Mendiola, Andrew S. ^{[4
]}

Jellison, Evan R. ^{[2
]}

Givogri, Maria I. ^{[5
]}

Han, David K. ^{[6
]}

Bongarzone, Ernesto R. ^{[5
]}

Akassoglou, Katerina ^{[4
,7
]}

Vella, Anthony T. ^{[2
]}

Crocker, Stephen J. ^{[1
]}

机构：

[1] Univ Connecticut, Sch Med, Dept Neurosci, Farmington, CT 06030 USA

[2] Univ Connecticut, Sch Med, Dept Immunol, Farmington, CT 06030 USA

[3] UConn Hlth, Inst Syst Genom, Farmington, CT 06030 USA

[4] Gladstone Inst Neurol Dis, San Francisco, CA 94158 USA

[5] Univ Illinois, Dept Anat & Cell Biol, Chicago, IL 60612 USA

[6] Univ Connecticut, Sch Med, Dept Cell Biol, Farmington, CT 06030 USA

[7] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2019年 / 116卷 / 21期

基金：

美国国家卫生研究院;

关键词：

autoimmunity; proteomics; EAE; T cell; relapse; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CD8(+) T-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; RESPONSES; CNS; PATHOGENESIS; MECHANISMS; PROTEINS; EXOSOMES; DISEASE;

D O I：

10.1073/pnas.1816911116

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Extracellular vesicles (EVs) are emerging as potent mediators of intercellular communication with roles in inflammation and disease. In this study, we examined the role of EVs from blood plasma (pEVs) in an experimental autoimmune encephalomyelitis mouse model of central nervous system demyelination. We determined that pEVs induced a spontaneous relapsing-remitting disease phenotype in MOG35-55-immunized C57BL/6 mice. This modified disease phenotype was found to be driven by CD8+ T cells and required fibrinogen in pEVs. Analysis of pEVs from relapsing-remitting multiple sclerosis patients also identified fibrinogen as a significant portion of pEV cargo. Together, these data suggest that fibrinogen in pEVs contributes to the perpetuation of neuroinflammation and relapses in disease.

引用

页码：10488 / 10493

页数：6

共 40 条

[1] Clonal expansions of CD8+ T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction [J].

Babbe, H ;

Roers, A ;

Waisman, A ;

Lassmann, H ;

Goebels, N ;

Hohlfeld, R ;

Friese, M ;

Schröder, R ;

Deckert, M ;

Schmidt, S ;

Ravid, R ;

Rajewsky, K .

JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (03) :393-404

[2] Characterization of Relapsing-Remitting and Chronic Forms of Experimental Autoimmune Encephalomyelitis in C57BL/6 Mice [J].

Berard, Jennifer L. ;

Wolak, Kevin ;

Fournier, Sylvie ;

David, Samuel .

GLIA, 2010, 58 (04) :434-445

[3] Genetics of experimental allergic encephalomyelitis supports the role of T helper cells in multiple sclerosis pathogenesis [J].

Blankenhorn, Elizabeth P. ;

Butterfield, Russell ;

Case, Laure K. ;

Wall, Emma H. ;

del Rio, Roxana ;

Diehl, Sean A. ;

Krementsov, Dimitry N. ;

Saligrama, Naresha ;

Teuscher, Cory .

ANNALS OF NEUROLOGY, 2011, 70 (06) :887-896

[4] Activated CD8+T cells in secondary progressive MS secrete lymphotoxin [J].

Buckle, GJ ;

Höllsberg, P ;

Hafler, DA .

NEUROLOGY, 2003, 60 (04) :702-705

[5] Biochemically altered myelin triggers autoimmune demyelination [J].

Caprariello, Andrew V. ;

Rogers, James A. ;

Morgan, Megan L. ;

Hoghooghi, Vahid ;

Plemel, Jason R. ;

Koebel, Adam ;

Tsutsui, Shigeki ;

Dunn, Jeffrey F. ;

Kotra, Lakshmi P. ;

Ousman, Shalina S. ;

Yong, V. Wee ;

Stys, Peter K. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2018, 115 (21) :5528-5533

[6] Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response [J].

Chen, Gang ;

Huang, Alexander C. ;

Zhang, Wei ;

Zhang, Gao ;

Wu, Min ;

Xu, Wei ;

Yu, Zili ;

Yang, Jiegang ;

Wang, Beike ;

Sun, Honghong ;

Xia, Houfu ;

Man, Qiwen ;

Zhong, Wenqun ;

Antelo, Leonardo F. ;

Wu, Bin ;

Xiong, Xuepeng ;

Liu, Xiaoming ;

Guan, Lei ;

Li, Ting ;

Liu, Shujing ;

Yang, Ruifeng ;

Lu, Youtao ;

Dong, Liyun ;

McGettigan, Suzanne ;

Somasundaram, Rajasekharan ;

Radhakrishnan, Ravi ;

Mills, Gordon ;

Lu, Yiling ;

Kim, Junhyong ;

Chen, Youhai H. ;

Dong, Haidong ;

Zhao, Yifang ;

Karakousis, Giorgos C. ;

Mitchell, Tara C. ;

Schuchter, Lynn M. ;

Herlyn, Meenhard ;

Wherry, E. John ;

Xu, Xiaowei ;

Guo, Wei .

NATURE, 2018, 560 (7718) :382-+

[7] Novel CD8+ Treg suppress EAE by TGF-β- and IFN-γ-dependent mechanisms [J].

Chen, Mei-Ling ;

Yan, Bo-Shiun ;

Kozoriz, Deneen ;

Weiner, Howard L. .

EUROPEAN JOURNAL OF IMMUNOLOGY, 2009, 39 (12) :3423-3435

[8] Exosomes from red blood cell units bind to monocytes and induce proinflammatory cytokines, boosting T-cell responses in vitro [J].

Danesh, Ali ;

Inglis, Heather C. ;

Jackman, Rachael P. ;

Wu, Shiquan ;

Deng, Xutao ;

Muench, Marcus O. ;

Heitman, John W. ;

Norris, Philip J. .

BLOOD, 2014, 123 (05) :687-696

[9] A SUPPRESSOR LYMPHOCYTE-T CELL-LINE FOR AUTOIMMUNE ENCEPHALOMYELITIS [J].

ELLERMAN, KE ;

POWERS, JM ;

BROSTOFF, SW .

NATURE, 1988, 331 (6153) :265-267

[10] Myelin oligodendrocyte glycoprotein peptide-induced experimental allergic encephalomyelitis and T cell responses are unaffected by immunoproteasome deficiency [J].

Frausto, Ricardo F. ;

Crocker, Stephen J. ;

Earn, Boreth ;

Whitmire, Jason K. ;

Whitton, J. Lindsay .

JOURNAL OF NEUROIMMUNOLOGY, 2007, 192 (1-2) :124-133

← 1 2 3 4 →