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

25Citations
Citations of this article
22Readers
Mendeley users who have this article in their library.
Get full text

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 Tregcells 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. © 2012 British Society for Immunology.

Cite

CITATION STYLE

APA

Lee, K., Hwang, S., Paik, D. J., Kim, W. K., Kim, J. M., & Youn, J. (2012). Bacillus-derived poly-γ-glutamic acid reciprocally regulates the differentiation of T helper 17 and regulatory T cells and attenuates experimental autoimmune encephalomyelitis. Clinical and Experimental Immunology, 170(1), 66–76. https://doi.org/10.1111/j.1365-2249.2012.04637.x

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free