A commensal symbiotic factor derived from Bacteroides fragilis promotes human CD39+Foxp3+ T cells and Treg function

Kiel M. Telesford, Wang Yan, Javier Ochoa-Reparaz, Anudeep Pant, Christopher Kircher, Marc A. Christy, Sakhina Begum-Haque, Dennis L. Kasper, Lloyd H. Kasper

Research output: Contribution to journalArticlepeer-review

199 Scopus citations

Abstract

Polysaccharide A (PSA) derived from the human commensal Bacteroides fragilis is a symbiosis factor that stimulates immunologic development within mammalian hosts. PSA rebalances skewed systemic T helper responses and promotes T regulatory cells (Tregs). However, PSA-mediated induction of Foxp3 in humans has not been reported. In mice, PSA-generated Foxp3+ Tregs dampen Th17 activity thereby facilitating bacterial intestinal colonization while the increased presence and function of these regulatory cells may guard against pathological organ-specific inflammation in hosts. We herein demonstrate that PSA induces expression of Foxp3 along with CD39 among naïve CD4 T cells in vitro while promoting IL-10 secretion. PSA-activated dendritic cells are essential for the mediation of this regulatory response. When cultured with isolated Foxp3+ Tregs, PSA enriched Foxp3 expression, enhanced the frequency of CD39+HLA-DR+ cells, and increased suppressive function as measured by decreased TNFα expression by LPS-stimulated monocytes. Our findings are the first to demonstrate in vitro induction of human CD4+Foxp3+ T cells and enhanced suppressive function of circulating Foxp3+ Tregs by a human commensal bacterial symbiotic factor. Use of PSA for the treatment of human autoimmune diseases, in particular multiple sclerosis and inflammatory bowel disease, may represent a new paradigm in the approach to treating autoimmune disease.

Original languageEnglish
Pages (from-to)234-242
Number of pages9
JournalGut Microbes
Volume6
Issue number4
DOIs
StatePublished - 1 Jan 2015

Keywords

  • Autoimmunity
  • Bacteroides fragilis
  • Commensal microbiota
  • Dendritic cell
  • Ectonuclease
  • Foxp3
  • Multiple sclerosis
  • T regulatory cells
  • Zwitterionic polysaccharide

EGS Disciplines

  • Biology

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