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

Title
Bacillus-derived poly-gamma-glutamic acid reciprocally regulates the differentiation of T helper 17 and regulatory T cells and attenuates experimental autoimmune encephalomyelitis
Author
황세진
Keywords
autoimmune disease; experimental autoimmune encephalomyelitis; poly-?-glutamic acid; regulatory T cells; Th17 cells; TRANSCRIPTION FACTOR FOXP3; MULTIPLE-SCLEROSIS; SCURFY MOUSE; PATHWAYS; T(H)17; BETA; GENERATION; EXPRESSION; INFLAMMATION; INDUCTION
Issue Date
2012-10
Publisher
WILEY-BLACKWELL, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
Citation
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, OCT 2012, 170(1), p66-p76, 11p.
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-?-glutamic acid (?-PGA) signals naive CD4+ T cells to promote the selective differentiation of Treg cells and to suppress the differentiation of Th17 cells. The ?-PGA inducibility of FoxP3 expression was due partially to transforming growth factor (TGF)-beta induction through a Toll-like receptor (TLR)-4/myeloid differentiating factor 88 (MyD88)-dependent pathway. However, this pathway was dispensable for ?-PGA suppression of Th17 differentiation. ?-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 ?t (ROR?t) while up-regulating the STAT-3 inhibitor suppressor of cytokine signalling 3 (SOCS3). Importantly, in vivo administration of ?-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, ?-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 ?-PGA for treating Th17 cell-mediated autoimmune diseases.
URI
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2249.2012.04637.xhttp://repository.hanyang.ac.kr/handle/20.500.11754/69425
ISSN
0009-9104
DOI
10.1111/j.1365-2249.2012.04637.x
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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