| First Author | Lee K | Year | 2012 |
| Journal | Clin Exp Immunol | Volume | 170 |
| Issue | 1 | Pages | 66-76 |
| PubMed ID | 22943202 | Mgi Jnum | J:188286 |
| Mgi Id | MGI:5440128 | Doi | 10.1111/j.1365-2249.2012.04637.x |
| Citation | Lee K, et al. (2012) Bacillus-derived poly-gamma-glutamic acid reciprocally regulates the differentiation of T helper 17 and regulatory T cells and attenuates experimental autoimmune encephalomyelitis. Clin Exp Immunol 170(1):66-76 |
| abstractText | Forkhead box protein 3 (FoxP3(+)) regulatory T (T(reg)) 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-gamma-glutamic acid (gamma-PGA) signals naive CD4(+) T cells to promote the selective differentiation of T(reg) cells and to suppress the differentiation of Th17 cells. The gamma-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 gamma-PGA suppression of Th17 differentiation. gamma-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 gammat (RORgammat) while up-regulating the STAT-3 inhibitor suppressor of cytokine signalling 3 (SOCS3). Importantly, in vivo administration of gamma-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, gamma-PGA, as a novel regulator of autoimmune responses, capable of promoting the differentiation of anti-inflammatory T(reg) cells and suppressing the differentiation of proinflammatory Th17 cells. These findings draw attention to the potential of gamma-PGA for treating Th17 cell-mediated autoimmune diseases. |
