Journal
SCIENCE IMMUNOLOGY
Volume 5, Issue 53, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciimmunol.abc7191
Keywords
-
Categories
Funding
- Swiss National Science Foundation [P2SKP3_164938/1, P300PB_177927/1]
- National MS Society (NMSS) fellowship (Kathleen C. Moore Fellowship) [FG-1708-28871]
- University of Basel
- Medical Faculty Mannheim, University of Heidelberg
- Hertie Foundation
- NMSS Clinician Scientist Development Award (Kathleen C. Moore Fellowship) [FAN-1507-05497]
- NMSS-American Brain Foundation (ABF) Clinician Scientist Development Award [FAN-1608-25607]
- National Institute of Neurological Disorders and Stroke [R35NS111644]
- Swedish Brain Foundation [2012-0262, 2012-0305, 2013-0279, 2016-0303]
- Swedish Science Council [2012-3167, 2017-03100]
- Knut and Alice Wallenberg Foundation [2012.0091, 2014.0305]
- Ulla-Carin Lindquist Foundation
- Umea University Insamlingsstiftelsen [223-2808-12, 223-1881-13, 2.1.12-1605-14]
- Vasterbotten County Council [56103-7002829]
- Swedish Brain Power
- King Gustaf V and Queen Victoria's Freemason's Foundation
- Max-Planck Society
- MS Society of Canada [3194]
- Canadian Institutes of Health Research [15992]
- Debbie and Andy Rachleff Foundation
- Hertie Foundation (medMS MyLab) [P1180016]
- NMSS [FG-1902-33617]
- Valhalla Charitable Foundation
- Heidrich Friends and Family endowed chair in Neurology at UCSF
- Swiss National Science Foundation (SNF) [P300PB_177927, P2SKP3_164938] Funding Source: Swiss National Science Foundation (SNF)
- Swedish Research Council [2017-03100] Funding Source: Swedish Research Council
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available