Bacillus-derived poly-γ-glutamic acid reciprocally regulates the differentiation of T helper 17 and regulatory T cells and attenuates experimental autoimmune encephalomyelitis

K. Lee, S. Hwang, D. J. Paik, W. K. Kim, J. M. Kim, J. Youn

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Forkhead box protein 3 (FoxP3+) regulatory T (Treg) cells and interleukin (IL)-17-producing T helper 17 (Th17) cells have opposing effects on autoimmunity, as the former are crucial for maintaining self-tolerance while the latter play a key role in precipitating inflammatory autoimmune diseases. Here we report that Bacillus-derived poly-γ-glutamic acid (γ-PGA) signals naive CD4+ T cells to promote the selective differentiation of Treg cells and to suppress the differentiation of Th17 cells. The γ-PGA inducibility of FoxP3 expression was due partially to transforming growth factor (TGF)-β induction through a Toll-like receptor (TLR)-4/myeloid differentiating factor 88 (MyD88)-dependent pathway. However, this pathway was dispensable for γ-PGA suppression of Th17 differentiation. γ-PGA inhibited IL-6-driven induction of Th17-specific factors including signal transducer and activator of transcription-3 (STAT-3) and retinoic acid-related orphan receptor γt (RORγt) while up-regulating the STAT-3 inhibitor suppressor of cytokine signalling 3 (SOCS3). Importantly, in vivo administration of γ-PGA attenuated the symptoms of experimental autoimmune encephalomyelitis and at the same time reduced Th17 cell infiltrates in the central nervous system. Thus, we have identified the microbe-associated molecular pattern, γ-PGA, as a novel regulator of autoimmune responses, capable of promoting the differentiation of anti-inflammatory Treg cells and suppressing the differentiation of proinflammatory Th17 cells. These findings draw attention to the potential of γ-PGA for treating Th17 cell-mediated autoimmune diseases.

Original languageEnglish
Pages (from-to)66-76
Number of pages11
JournalClinical and Experimental Immunology
Volume170
Issue number1
DOIs
Publication statusPublished - 2012 Oct 1
Externally publishedYes

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Keywords

  • Autoimmune disease
  • Experimental autoimmune encephalomyelitis
  • Poly-γ-glutamic acid
  • Regulatory T cells
  • Th17 cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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