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

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...

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Main Authors: Pröbstel, Anne-Katrin (Author) , Zhou, Xiaoyuan (Author) , Baumann, Ryan (Author) , Wischnewski, Sven (Author) , Kutza, Michael (Author) , Rojas, Olga L. (Author) , Sellrie, Katrin (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 (Author) , Tran, Edwina B. (Author) , Barba, Patrick (Author) , Zorn, Kelsey (Author) , Oechtering, Johanna (Author) , Forsberg, Karin (Author) , Shiow, Lawrence R. (Author) , Henry, Roland G. (Author) , Graves, Jennifer (Author) , Cree, Bruce A. C. (Author) , Hauser, Stephen L. (Author) , Kuhle, Jens (Author) , Gelfand, Jeffrey M. (Author) , Andersen, Peter M. (Author) , Schlegel, Jürgen (Author) , Turnbaugh, Peter J. (Author) , Seeberger, Peter H. (Author) , Gommerman, Jennifer L. (Author) , Wilson, Michael R. (Author) , Schirmer, Lucas (Author) , Baranzini, Sergio E. (Author)
Format: Article (Journal)
Language:English
Published: November 2020
In: Science immunology
Year: 2020, Volume: 5, Issue: 53, Pages: 1-13
ISSN:2470-9468
DOI:10.1126/sciimmunol.abc7191
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1126/sciimmunol.abc7191
Verlag, lizenzpflichtig, Volltext: https://www.science.org/doi/10.1126/sciimmunol.abc7191
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Author Notes:Anne-Katrin Pröbstel, Xiaoyuan Zhou, Ryan Baumann, Sven Wischnewski, Michael Kutza, Olga L. Rojas, Katrin Sellrie, Antje Bischof, Kicheol Kim, Akshaya Ramesh, Ravi Dandekar, Ariele L. Greenfield, Ryan D. Schubert, Jordan E. Bisanz, Stephanie Vistnes, Khashayar Khaleghi, James Landefeld, Gina Kirkish, Friederike Liesche-Starnecker, Valeria Ramaglia, Sneha Singh, Edwina B. Tran, Patrick Barba, Kelsey Zorn, Johanna Oechtering, Karin Forsberg, Lawrence R. Shiow, Roland G. Henry, Jennifer Graves, Bruce A. C. Cree, Stephen L. Hauser, Jens Kuhle, Jeffrey M. Gelfand, Peter M. Andersen, Jürgen Schlegel, Peter J. Turnbaugh, Peter H. Seeberger, Jennifer L. Gommerman, Michael R. Wilson, Lucas Schirmer, Sergio E. Baranzini
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Summary: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.
Item Description:Online veröffentlicht: 13. November 2020
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Gesehen am 29.05.2024
Physical Description:Online Resource
ISSN:2470-9468
DOI:10.1126/sciimmunol.abc7191

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