Expression of leukotriene B 4 receptor 1 defines functionally distinct DCs that control allergic skin inflammation

Leukotriene B (LTB ) receptor 1 (BLT1) is a chemotactic G protein-coupled receptor expressed by leukocytes, such as granulocytes, macrophages, and activated T cells. Although there is growing evidence that BLT1 plays crucial roles in immune responses, its role in dendritic cells remains largely unkn...

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Veröffentlicht in:Cellular & molecular immunology 2021-06, Vol.18 (6), p.1437
Hauptverfasser: Koga, Tomoaki, Sasaki, Fumiyuki, Saeki, Kazuko, Tsuchiya, Soken, Okuno, Toshiaki, Ohba, Mai, Ichiki, Takako, Iwamoto, Satoshi, Uzawa, Hirotsugu, Kitajima, Keiko, Meno, Chikara, Nakamura, Eri, Tada, Norihiro, Fukui, Yoshinori, Kikuta, Junichi, Ishii, Masaru, Sugimoto, Yukihiko, Nakao, Mitsuyoshi, Yokomizo, Takehiko
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container_issue 6
container_start_page 1437
container_title Cellular & molecular immunology
container_volume 18
creator Koga, Tomoaki
Sasaki, Fumiyuki
Saeki, Kazuko
Tsuchiya, Soken
Okuno, Toshiaki
Ohba, Mai
Ichiki, Takako
Iwamoto, Satoshi
Uzawa, Hirotsugu
Kitajima, Keiko
Meno, Chikara
Nakamura, Eri
Tada, Norihiro
Fukui, Yoshinori
Kikuta, Junichi
Ishii, Masaru
Sugimoto, Yukihiko
Nakao, Mitsuyoshi
Yokomizo, Takehiko
description Leukotriene B (LTB ) receptor 1 (BLT1) is a chemotactic G protein-coupled receptor expressed by leukocytes, such as granulocytes, macrophages, and activated T cells. Although there is growing evidence that BLT1 plays crucial roles in immune responses, its role in dendritic cells remains largely unknown. Here, we identified novel DC subsets defined by the expression of BLT1, namely, BLT1 and BLT1 DCs. We also found that BLT1 and BLT1 DCs differentially migrated toward LTB and CCL21, a lymph node-homing chemoattractant, respectively. By generating LTB -producing enzyme LTA H knockout mice and CD11c promoter-driven Cre recombinase-expressing BLT1 conditional knockout (BLT1 cKO) mice, we showed that the migration of BLT1 DCs exacerbated allergic contact dermatitis. Comprehensive transcriptome analysis revealed that BLT1 DCs preferentially induced Th1 differentiation by upregulating IL-12p35 expression, whereas BLT1 DCs accelerated T cell proliferation by producing IL-2. Collectively, the data reveal an unexpected role for BLT1 as a novel DC subset marker and provide novel insights into the role of the LTB -BLT1 axis in the spatiotemporal regulation of distinct DC subsets.
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Although there is growing evidence that BLT1 plays crucial roles in immune responses, its role in dendritic cells remains largely unknown. Here, we identified novel DC subsets defined by the expression of BLT1, namely, BLT1 and BLT1 DCs. We also found that BLT1 and BLT1 DCs differentially migrated toward LTB and CCL21, a lymph node-homing chemoattractant, respectively. By generating LTB -producing enzyme LTA H knockout mice and CD11c promoter-driven Cre recombinase-expressing BLT1 conditional knockout (BLT1 cKO) mice, we showed that the migration of BLT1 DCs exacerbated allergic contact dermatitis. Comprehensive transcriptome analysis revealed that BLT1 DCs preferentially induced Th1 differentiation by upregulating IL-12p35 expression, whereas BLT1 DCs accelerated T cell proliferation by producing IL-2. Collectively, the data reveal an unexpected role for BLT1 as a novel DC subset marker and provide novel insights into the role of the LTB -BLT1 axis in the spatiotemporal regulation of distinct DC subsets.</abstract><cop>China</cop><pmid>33037399</pmid><orcidid>https://orcid.org/0000-0002-4215-007X</orcidid><orcidid>https://orcid.org/0000-0002-5219-1553</orcidid><orcidid>https://orcid.org/0000-0001-5605-2158</orcidid></addata></record>
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source MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection
subjects Animals
Biomarkers - metabolism
Cell Differentiation - drug effects
Cell Membrane - drug effects
Cell Membrane - metabolism
Cell Movement - drug effects
Cell Proliferation - drug effects
Chemokine CCL21 - pharmacology
Dendritic Cells - drug effects
Dendritic Cells - metabolism
Dermatitis, Atopic - complications
Dermatitis, Atopic - immunology
Dermatitis, Atopic - pathology
Hypersensitivity - complications
Hypersensitivity - immunology
Hypersensitivity - pathology
Inflammation - complications
Inflammation - immunology
Inflammation - pathology
Interleukin-12 - biosynthesis
Leukotriene B4 - metabolism
Lymph Nodes - drug effects
Mice
Mice, Inbred C57BL
Receptors, Leukotriene B4 - metabolism
Skin - pathology
Th1 Cells - drug effects
Th1 Cells - immunology
Transcriptome - genetics
title Expression of leukotriene B 4 receptor 1 defines functionally distinct DCs that control allergic skin inflammation
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