Expression of leukotriene B4 receptor 1 defines functionally distinct DCs that control allergic skin inflammation
| Autor: | Yukihiko Sugimoto, Eri Nakamura, Yoshinori Fukui, Mitsuyoshi Nakao, Soken Tsuchiya, Norihiro Tada, Fumiyuki Sasaki, Masaru Ishii, Keiko Kitajima, Satoshi Iwamoto, Kazuko Saeki, Chikara Meno, Toshiaki Okuno, Hirotsugu Uzawa, Tomoaki Koga, Takako Ichiki, Mai Ohba, Junichi Kikuta, Takehiko Yokomizo |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
BLT1 Leukotriene B4 T cell Immunology Receptors Leukotriene B4 CD11c Inflammation Biology Article Dermatitis Atopic 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Movement Conditional gene knockout Hypersensitivity medicine Animals Immunology and Allergy dendritic cells lipid mediator Receptor Cell Proliferation Skin Chemokine CCL21 Cell Membrane hemic and immune systems Cell Differentiation Leukotriene B4 Receptor 1 Th1 Cells Interleukin-12 Cell biology Mice Inbred C57BL Gene regulation in immune cells 030104 developmental biology Infectious Diseases medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis LTB4 Lymph Nodes medicine.symptom Transcriptome Biomarkers CCL21 |
| Zdroj: | Cellular and Molecular Immunology |
| ISSN: | 2042-0226 1672-7681 |
| DOI: | 10.1038/s41423-020-00559-7 |
| Popis: | Leukotriene B4 (LTB4) 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, BLT1hi and BLT1lo DCs. We also found that BLT1hi and BLT1lo DCs differentially migrated toward LTB4 and CCL21, a lymph node-homing chemoattractant, respectively. By generating LTB4-producing enzyme LTA4H knockout mice and CD11c promoter-driven Cre recombinase-expressing BLT1 conditional knockout (BLT1 cKO) mice, we showed that the migration of BLT1hi DCs exacerbated allergic contact dermatitis. Comprehensive transcriptome analysis revealed that BLT1hi DCs preferentially induced Th1 differentiation by upregulating IL-12p35 expression, whereas BLT1lo 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 LTB4-BLT1 axis in the spatiotemporal regulation of distinct DC subsets. |
| Databáze: | OpenAIRE |
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