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International Immunology Advance Access published online on June 26, 2009

International Immunology, doi:10.1093/intimm/dxp065
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© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Bacillus subtilis-specific poly-{gamma}-glutamic acid regulates development pathways of naive CD4+ T cells through antigen-presenting cell-dependent and -independent mechanisms

Sunghoon Kim1,*, Jun Young Yang2,*, Kyuheon Lee1, Kyu Heon Oh2, Mia Gi2, Jung Mogg Kim3, Doo Jin Paik1, Seokmann Hong2 and Jeehee Youn1

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

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-{gamma}-glutamic acid ({gamma}-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 {gamma}-PGA during priming promoted the development of Th1 and Th17 cells but inhibited development of Th2 cells. {gamma}-PGA up-regulated the expression of T-bet and ROR-{gamma}t, the master genes of Th1 and Th17 cells, respectively, whereas down-regulating the level of GATA-3, the master gene of Th2 cells. {gamma}-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 {gamma}-PGA on Th1/Th2 development was dependent on the presence of antigen-presenting cells (APC). Furthermore, {gamma}-PGA-stimulated DC favored the polarization of naive CD4+ T cells toward Th1 cells rather than Th2 cells. In contrast, {gamma}-PGA affected Th17 cell development, regardless of the presence or absence of APC. Thus, these data demonstrate that {gamma}-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-{gamma}-glutamic acid, Th


* These authors are co-first authors

Transmitting editor: K. Yamamoto

Received 24 April 2008, accepted 5 June 2009.


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