Recirculating Intestinal IgA-Producing Cells Regulate Neuroinflammation via IL-10

被引：242

作者：

Rojas, Olga L. ^{[1
]}

Probstel, Anne-Katrin ^{[2
,3
]}

Porfilio, Elisa A. ^{[1
]}

Wang, Angela A. ^{[1
]}

Charabati, Marc ^{[4
,5
]}

Sun, Tian ^{[1
]}

Lee, Dennis S. W. ^{[1
]}

Galicia, Georgina ^{[1
]}

Ramaglia, Valeria ^{[1
]}

Ward, Lesley A. ^{[1
]}

Leung, Leslie Y. T. ^{[1
]}

Najafi, Ghazal ^{[1
]}

Khaleghi, Khashayar ^{[1
]}

Garcillan, Beatriz ^{[6
]}

Li, Angela ^{[1
,7
]}

Besla, Rickvinder ^{[7
,8
]}

Naouar, Ikbel ^{[1
]}

Cao, Eric Y. ^{[1
]}

Chiaranunt, Pailin ^{[1
]}

Burrows, Kyle ^{[1
]}

Robinson, Hannah G. ^{[9
]}

Allanach, Jessica R. ^{[9
]}

Yam, Jennifer ^{[1
]}

Luck, Helen ^{[1
,7
]}

Campbell, Daniel J. ^{[10
,11
]}

Allman, David ^{[12
]}

Brooks, David G. ^{[1
,13
]}

Tomura, Michio ^{[14
]}

Baumann, Ryan ^{[2
,3
]}

Zamvil, Scott S. ^{[2
,3
,15
]}

Bar-Or, Amit ^{[16
]}

Horwitz, Marc S. ^{[8
]}

Winer, Daniel A. ^{[7
,8
]}

Mortha, Arthur ^{[1
]}

Mackay, Fabienne ^{[6
]}

Prat, Alexandre ^{[4
,5
]}

Osborne, Lisa C. ^{[9
]}

Robbins, Clinton ^{[1
,7
,8
]}

Baranzini, Sergio E. ^{[2
,3
,17
,18
]}

Gommerman, Jennifer L. ^{[1
]}

机构：

[1] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada

[2] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA

[3] Univ Calif San Francisco, Weill Inst Neurosci, San Francisco, CA 94158 USA

[4] Univ Montreal, Fac Med, CRCHUM, Neuroimmunol Unit, Montreal, PQ H2X 0A9, Canada

[5] Univ Montreal, Fac Med, Dept Neurosci, Montreal, PQ H2X 0A9, Canada

[6] Univ Melbourne, Sch Biomed Sci, Parkville, Vic 3010, Australia

[7] Toronto Gen Res Inst, Univ Hlth Network, Toronto, ON M5G 2C4, Canada

[8] Univ Toronto, Dept Lab & Med Pathol, Toronto, ON M5S 1A8, Canada

[9] Univ British Columbia, Life Sci Inst, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z3, Canada

[10] Univ Washington, Sch Med, Benaroya Res Inst, Seattle, WA 98101 USA

[11] Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98101 USA

[12] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[13] Princess Margaret Canc Ctr, Univ Hlth Network, Toronto, ON M5G 2M9, Canada

[14] Osaka Ohtani Univ, Fac Pharm, Lab Immunol, Tondabayashi, Osaka 5848540, Japan

[15] Univ Calif San Francisco, Program Immunol, San Francisco, CA 94143 USA

[16] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA

[17] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA

[18] Univ Calif San Francisco, Grad Program Bioinformat, San Francisco, CA 94143 USA

来源：

CELL | 2019年 / 176卷 / 03期

基金：

加拿大健康研究院; 瑞士国家科学基金会;

关键词：

B-CELLS; MULTIPLE-SCLEROSIS; PLASMA-CELLS; T-CELLS; AUTOIMMUNE; ATACICEPT; RESPONSES; BACTERIA; PROTECT; EXPRESSION;

D O I：

10.1016/j.cell.2018.11.035

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Plasma cells (PC) are found in the CNS of multiple sclerosis (MS) patients, yet their source and role in MS remains unclear. We find that some PC in the CNS of mice with experimental autoimmune encephalomyelitis (EAE) originate in the gut and produce immunoglobulin A (IgA). Moreover, we show that IgA(+) PC are dramatically reduced in the gut during EAE, and likewise, a reduction in IgA-bound fecal bacteria is seen in MS patients during disease relapse. Removal of plasmablast (PB) plus PC resulted in exacerbated EAE that was normalized by the introduction of gut-derived IgA(+) PC. Furthermore, mice with an over-abundance of IgA(+) PB and/or PC were specifically resistant to the effector stage of EAE, and expression of interleukin (IL)-10 by PB plus PC was necessary and sufficient to confer resistance. Our data show that IgA(+) PB and/or PC mobilized from the gut play an unexpected role in suppressing neuroinflammation.

引用

页码：610 / +

页数：33

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