International Immunology Advance Access originally published online on June 26, 2009
International Immunology 2009 21(8):977-990; doi:10.1093/intimm/dxp065
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Bacillus subtilis-specific poly-
-glutamic acid regulates development pathways of naive CD4+ T cells through antigen-presenting cell-dependent and -independent mechanisms
1 Department of Anatomy and Cell Biology, Institute of Biomedical Science, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, Korea
2 Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, 98 Kunja-dong, Kwangjin-gu, Seoul 143-747, Korea
3 Department of Microbiology, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, Seoul, Korea
Correspondence to: J. Youn; E-mail: jhyoun{at}hanyang.ac.kr, and S. Hong; E-mail: shong{at}sejong.ac.kr
Peripheral naive CD4+ T cells selectively differentiate to type 1 Th, type 2 Th and IL-17-producing Th (Th17) cells, depending on the priming conditions. Since these subsets develop antagonistically to each other to elicit subset-specific adaptive immune responses, balance between these subsets can regulate the susceptibility to diverse immune diseases. The present study was undertaken to determine whether poly-
-glutamic acid (
-PGA), an edible and safe exopolymer that is generated by microorganisms such as Bacillus subtilis, could modulate the development pathways of Th subsets. The presence of
-PGA during priming promoted the development of Th1 and Th17 cells but inhibited development of Th2 cells.
-PGA up-regulated the expression of T-bet and ROR-
t, the master genes of Th1 and Th17 cells, respectively, whereas down-regulating the level of GATA-3, the master gene of Th2 cells.
-PGA induced the expression of IL-12p40, CD80 and CD86 in dendritic cells (DC) and macrophages in a Toll-like receptor-4-dependent manner, and the effect of
-PGA on Th1/Th2 development was dependent on the presence of antigen-presenting cells (APC). Furthermore,
-PGA-stimulated DC favored the polarization of naive CD4+ T cells toward Th1 cells rather than Th2 cells. In contrast,
-PGA affected Th17 cell development, regardless of the presence or absence of APC. Thus, these data demonstrate that
-PGA has the potential to regulate the development pathways of naive CD4+ T cells through APC-dependent and -independent mechanisms and to be applicable to treating Th2-dominated diseases.
Keywords: antigen-presenting cells, Bacillus subtilis, poly-
-glutamic acid, Th
* These authors are co-first authors
Transmitting editor: K. Yamamoto
Received 24 April 2008, accepted 5 June 2009.