Effects of prostaglandin D2 on helper T cell functions.
Prostaglandin (PG) D(2) is abundantly produced by mast cells in the sites of allergic inflammations and acts on various cell types through its receptors DP and CRTH2. Among human T cells, CRTH2 is preferentially expressed on Th2-type cells. However, distribution of DP among T cells and impacts of CRTH2- and DP-mediated signals on T cell functions are presently unclear. Here, we show that CD4(+) and CD8(+) T cells producing IFN-gamma and IL-2 were reduced by DP-mediated signals, while CRTH2-mediated signals enhanced IL-2, IL-4, IL-5, and IL-13 production by Th2 cells. CRTH2 signals also caused up-regulation of CD11b and CD40L in resting Th2 cells. RT-PCR analysis revealed distribution of DP among Th cell subsets. On CRTH2(+) Th2 cells, the CRTH2-mediated PGD(2) effects were dominantly observed. Thus, PGD(2) favors Th2 functions through CRTH2 while restraining Th1 functions via DP, which may contribute to development of Th2-dominated status in allergic inflammations.
Tanaka
Kazuya
K
Department of Advanced Medicine and Development, BML, Inc., Saitama 350-1101, Japan.
Hirai
Hiroyuki
H
Takano
Shoichi
S
Nakamura
Masataka
M
Nagata
Kinya
K
D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D015230:Prostaglandin D2 / Q000494:pharmacology*; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000378:metabolism*
D016207:Cytokines; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D015847:Interleukin-4; D007371:Interferon-gamma; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor