PMID- 20004699 OWN - NLM STAT- MEDLINE DCOM- 20100902 LR - 20100531 IS - 1638-6183 (Electronic) IS - 0300-9084 (Linking) VI - 92 IP - 6 DP - 2010 Jun TI - Attenuated Th1 induction by dendritic cells from mice deficient in the leukotriene B4 receptor 1. PG - 682-91 LID - 10.1016/j.biochi.2009.12.002 [doi] AB - 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 naive 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. CI - Copyright 2010 Elsevier Masson SAS. All rights reserved. FAU - Toda, Akiko AU - Toda A AD - Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. FAU - Terawaki, Kan AU - Terawaki K FAU - Yamazaki, Soh AU - Yamazaki S FAU - Saeki, Kazuko AU - Saeki K FAU - Shimizu, Takao AU - Shimizu T FAU - Yokomizo, Takehiko AU - Yokomizo T LA - eng PT - Journal Article DEP - 20091223 PL - France TA - Biochimie JT - Biochimie JID - 1264604 RN - 0 (Ltb4r1 protein, mouse) RN - 0 (Receptors, Leukotriene B4) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Cell Differentiation MH - Dendritic Cells/cytology/*immunology/metabolism MH - Interferon-gamma/metabolism MH - Mice MH - Mice, Inbred Strains MH - Receptors, Leukotriene B4/*genetics/metabolism MH - Th1 Cells/*immunology EDAT- 2009/12/17 06:00 MHDA- 2010/09/03 06:00 CRDT- 2009/12/17 06:00 PHST- 2009/09/25 00:00 [received] PHST- 2009/12/02 00:00 [accepted] PHST- 2009/12/17 06:00 [entrez] PHST- 2009/12/17 06:00 [pubmed] PHST- 2010/09/03 06:00 [medline] AID - S0300-9084(09)00333-2 [pii] AID - 10.1016/j.biochi.2009.12.002 [doi] PST - ppublish SO - Biochimie. 2010 Jun;92(6):682-91. doi: 10.1016/j.biochi.2009.12.002. Epub 2009 Dec 23.