Attenuated Th1 induction by dendritic cells from mice deficient in the leukotriene B4 receptor 1.
Dendritic cells (DCs) are important antigen-presenting cells that control Th1- and Th2-type immunological reactions by releasing cytokines and interacting directly with T cells. Leukotriene B4 (LTB4), a classical proinflammatory lipid mediator for phagocytes, was recently identified as an important attractant for effector CD4(+) and CD8(+) T cells. However, little information is available on the roles of LTB4 and its receptor BLT1 in DCs. Here we show that functional BLT1 expressed in mouse bone marrow-derived DCs (BMDCs) plays important role in initiating Th1-type immune response. Detailed analyses using BMDCs revealed that BLT1-deficient DCs produced less IL-12p70 than WT DCs, leading to attenuated IFN-gamma production in an allogeneic mixed lymphocyte reaction. Adoptive transfer of antigen-loaded BLT1-deficient DCs into naïve WT mice induced a weakened Th1- and enhanced Th2-response in vivo compared to WT DCs. BLT1-deficient mice consistently showed much attenuated delayed-type hypersensitivity (DTH), in which Th1-type cellular responses play a key role, and popliteal lymph node cells of BLT1-deficient mice showed reduced production of Th1 cytokines after DTH induction compared to cells from WT mice. Thus, in addition to its role in inflammation, the LTB4-BLT1 axis is important in initiating Th1-type immunological reactions mediated by DCs.
Toda
Akiko
A
Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Terawaki
Kan
K
Yamazaki
Soh
S
Saeki
Kazuko
K
Shimizu
Takao
T
Yokomizo
Takehiko
T
D000818:Animals; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018102:Receptors, Leukotriene B4 / Q000235:genetics* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*
C503704:Ltb4r1 protein, mouse; D018102:Receptors, Leukotriene B4; D007371:Interferon-gamma