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

Authors :
Jordan E. Bisanz
Edwina B. Tran
Patrick Barba
Ryan Baumann
Jennifer L. Gommerman
Michael R. Wilson
Lawrence R. Shiow
Jürgen Schlegel
Michael Kutza
Sergio E. Baranzini
Johanna Oechtering
James Landefeld
Jeffrey M. Gelfand
Jennifer Graves
Ryan D. Schubert
Friederike Liesche-Starnecker
Valeria Ramaglia
Lucas Schirmer
Kelsey C. Zorn
Kicheol Kim
Karin Forsberg
Stephen L. Hauser
Xiaoyuan Zhou
Jens Kuhle
Katrin Sellrie
Roland G. Henry
Khashayar Khaleghi
Akshaya Ramesh
Stephanie Vistnes
Bruce A.C. Cree
Peter M. Andersen
Peter J. Turnbaugh
Gina Kirkish
Peter H. Seeberger
Sven Wischnewski
Olga L. Rojas
Ariele L. Greenfield
Anne-Katrin Pröbstel
Ravi Dandekar
Sneha Singh
Antje Bischof
Source :
Science Immunology. 5
Publication Year :
2020
Publisher :
American Association for the Advancement of Science (AAAS), 2020.

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.

Details

ISSN :
24709468
Volume :
5
Database :
OpenAIRE
Journal :
Science Immunology
Accession number :
edsair.doi...........800a2771ca9f520b72d86f2e52d86f5b
Full Text :
https://doi.org/10.1126/sciimmunol.abc7191