Bacillus-derived poly-gamma-glutamic acid reciprocally regulates the differentiation of T helper 17 and regulatory T cells and attenuates experimental autoimmune encephalomyelitis
- Authors
- Lee, K.; Hwang, Se Jin; Paik, Doo Jin; Kim, Won Kyu; Kim, Jung Mogg; Youn, Jee hee
- Issue Date
- Oct-2012
- Publisher
- WILEY
- Keywords
- autoimmune disease; experimental autoimmune encephalomyelitis; poly-?-glutamic acid; regulatory T cells; Th17 cells
- Citation
- CLINICAL AND EXPERIMENTAL IMMUNOLOGY, v.170, no.1, pp.66 - 76
- Indexed
- SCIE
SCOPUS
- Journal Title
- CLINICAL AND EXPERIMENTAL IMMUNOLOGY
- Volume
- 170
- Number
- 1
- Start Page
- 66
- End Page
- 76
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/164533
- DOI
- 10.1111/j.1365-2249.2012.04637.x
- ISSN
- 0009-9104
- 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.
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