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  Gut microbiota-specific IgA+ B cells traffic to the CNS in active multiple sclerosis

Pröbstel, A.-K., Zhou, X., Baumann, R., Wischnewski, S., Kutza, M., Rojas, O. L., et al. (2020). Gut microbiota-specific IgA+ B cells traffic to the CNS in active multiple sclerosis. Science Immunology, 5(53): eabc7191. doi:10.1126/sciimmunol.abc7191.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0007-7E2F-9 Version Permalink: http://hdl.handle.net/21.11116/0000-0007-7E35-1
Genre: Journal Article

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 Creators:
Pröbstel, Anne-Katrin, Author
Zhou, Xiaoyuan, Author
Baumann, Ryan, Author
Wischnewski, Sven, Author
Kutza, Michael, Author
Rojas, Olga L., Author
Sellrie, Katrin1, Author              
Bischof, Antje, Author
Kim, Kicheol, Author
Ramesh, Akshaya, Author
Dandekar, Ravi, Author
Greenfield, Ariele L., Author
Schubert, Ryan D., Author
Bisanz, Jordan E., Author
Vistnes, Stephanie, Author
Khaleghi, Khashayar, Author
Landefeld, James, Author
Kirkish, Gina, Author
Liesche-Starnecker, Friederike, Author
Ramaglia, Valeria, Author
Singh, Sneha, AuthorTran, Edwina B., AuthorBarba, Patrick, AuthorZorn, Kelsey, AuthorOechtering, Johanna, AuthorForsberg, Karin, AuthorShiow, Lawrence R., AuthorHenry, Roland G., AuthorGraves, Jennifer, AuthorCree, Bruce A. C., AuthorHauser, Stephen L., AuthorKuhle, Jens, AuthorGelfand, Jeffrey M., AuthorAndersen, Peter M., AuthorSchlegel, Jürgen, AuthorTurnbaugh, Peter J., AuthorSeeberger, Peter H.2, Author              Gommerman, Jennifer L., AuthorWilson, Michael R., AuthorSchirmer, Lucas, AuthorBaranzini, Sergio E., Author more..
Affiliations:
1Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863286              
2Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863308              

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 Abstract: Changes in gut microbiota composition and a diverse role of B cells have recently been implicated in multiple sclerosis (MS), a central nervous system (CNS) autoimmune disease. Immunoglobulin A (IgA) is a key regulator at the mucosal interface. However, whether gut microbiota shape IgA responses and what role IgA+ cells have in neuroinflammation are unknown. Here, we identify IgA-bound taxa in MS and show that IgA-producing cells specific for MS-associated taxa traffic to the inflamed CNS, resulting in a strong, compartmentalized IgA enrichment in active MS and other neuroinflammatory diseases. Unlike previously characterized polyreactive anti-commensal IgA responses, CNS IgA cross-reacts with surface structures on specific bacterial strains but not with brain tissue. These findings establish gut microbiota–specific IgA+ cells as a systemic mediator in MS and suggest a critical role of mucosal B cells during active neuroinflammation with broad implications for IgA as an informative biomarker and IgA-producing cells as an immune subset to harness for therapeutic interventions.

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Language(s): eng - English
 Dates: 2020-11-202020
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1126/sciimmunol.abc7191
BibTex Citekey: Pröbsteleabc7191
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Title: Science Immunology
Source Genre: Journal
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Publ. Info: Washington, DC : Amercian Association for the Advancement of Science
Pages: - Volume / Issue: 5 (53) Sequence Number: eabc7191 Start / End Page: - Identifier: ISSN: 2470-9468