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Regulatory B cell induction by the gut microbiome protects against CNS inflammation and demyelination
Author(s): ,
Y Wang
Affiliations:
Microbiology/Immunology, Dartmouth Medical School, Hanover, NH
,
S Colpitts
Affiliations:
Microbiology/Immunology, Dartmouth Medical School, Hanover, NH
,
J Ochoa-Reparaz
Affiliations:
Biology, Eastern Washington University, Cheney, WA, United States
,
E Kaspetr
Affiliations:
Microbiology/Immunology, Dartmouth Medical School, Hanover, NH
,
K Telesford
Affiliations:
Microbiology/Immunology, Dartmouth Medical School, Hanover, NH
L Kasper
Affiliations:
Microbiology/Immunology, Dartmouth Medical School, Hanover, NH
ECTRIMS Online Library. Kasper L. Sep 16, 2016; 147028
Lloyd Kasper
Lloyd Kasper
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Abstract: 181

Type: Oral

Abstract Category: Pathology and pathogenesis of MS - Immunology

B lymphocytes have the ability to provide both positive and negative regulation of host immunity. While the classic antibody-mediated functions of B cells drive inflammation, regulatory B cells (Bregs) are involved in the maintenance of immune homeostasis during inflammation. While phenotypically heterogeneous, Bregs can be commonly identified by their production of the immunosuppressive cytokine interleukin-10 (IL-10). While artificial and exogenous microbial stimuli of Bregs have been described, environmental and endogenous cues for the induction of Bregs have yet to be described. Previous reports from our lab have identified that modulation of the microbiome during experimental autoimmune encephalomyelitis (EAE) leads to the induction of CD5+ Breg cells that can significantly reduce EAE disease severity. Here we show that treatment with polysaccharide A (PSA) derived from the intestinal symbiont Bacteroides fragilis also promotes an increase in systemic CD5+ Bregs following the onset of EAE. PSA-induced CD5+ Bregs produced IL-10 and were able to protect naïve recipients against EAE upon adoptive transfer. Specific deletion of IL-10 within B cells using IL-10fl/flCD19-Cre transgenics abrogated the protective effect of PSA. Importantly, we found that IL-10 production by B cells was dependent on TLR2 expression in vitro. In vivo, PSA was unable to modulate EAE disease severity when the B cell compartment was deficient in MyD88 signaling suggesting a B cell-intrinsic requirement for the ability to detect and respond to the intestinal microbiome. We have shown that the regulatory functions of B cells triggered by a specific gut commensal can restrain autoimmune inflammation affecting the CNS.

Disclosure: This work was supported by grants from the NMSS and NIH

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