Bacillus subtilis-specific poly-gamma-glutamic acid regulates development pathways of naive CD4(+) T cells through antigen-presenting cell-dependent and -independent mechanisms.
Peripheral naive CD4(+) T cells selectively differentiate to type 1 T(h), type 2 T(h) and IL-17-producing T(h) (T(h)17) 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 T(h) subsets. The presence of gamma-PGA during priming promoted the development of T(h)1 and T(h)17 cells but inhibited development of T(h)2 cells. gamma-PGA up-regulated the expression of T-bet and ROR-gammat, the master genes of T(h)1 and T(h)17 cells, respectively, whereas down-regulating the level of GATA-3, the master gene of T(h)2 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 T(h)1/T(h)2 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 T(h)1 cells rather than T(h)2 cells. In contrast, gamma-PGA affected T(h)17 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 T(h)2-dominated diseases.
Kim
Sunghoon
S
Department of Anatomy and Cell Biology, Institute of Biomedical Science, Hanyang University, Sungdong-Gu, Seoul, Korea.
Yang
Jun Young
JY
Lee
Kyuheon
K
Oh
Kyu Heon
KH
Gi
Mia
M
Kim
Jung Mogg
JM
Paik
Doo Jin
DJ
Hong
Seokmann
S
Youn
Jeehee
J
D000818:Animals; D017951:Antigen Presentation; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen / Q000096:biosynthesis; D001412:Bacillus subtilis / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis; D038041:Lymphopoiesis / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D053762:Interleukin-12 Subunit p40; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid