Expression of leukotriene B4 receptor 1 defines functionally distinct DCs that control allergic skin inflammation.

Abstract

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.

• Authors: Tomoaki Koga, Fumiyuki Sasaki, Kazuko Saeki, Soken Tsuchiya, Toshiaki Okuno, Mai Ohba, Takako Ichiki, Satoshi Iwamoto, Hirotsugu Uzawa, Keiko Kitajima, Chikara Meno, Eri Nakamura, Norihiro Tada, Yoshinori Fukui, Junichi Kikuta, Masaru Ishii, Yukihiko Sugimoto, Mitsuyoshi Nakao, Takehiko Yokomizo
• Journal: Cellular & molecular immunology (Cell Mol Immunol) Vol. 18 Issue 6 Pg. 1437-1449 (06 2021) ISSN: 2042-0226 [Electronic] China
• PMID: 33037399 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Chemokine CCL21
• Receptors, Leukotriene B4
• Interleukin-12
• Leukotriene B4

Topics

• Animals
• Biomarkers (metabolism)
• Cell Differentiation (drug effects)
• Cell Membrane (drug effects, metabolism)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Chemokine CCL21 (pharmacology)
• Dendritic Cells (drug effects, metabolism)
• Dermatitis, Atopic (complications, immunology, pathology)
• Hypersensitivity (complications, immunology, pathology)
• Inflammation (complications, immunology, pathology)
• Interleukin-12 (biosynthesis)
• Leukotriene B4 (metabolism)
• Lymph Nodes (drug effects)
• Mice, Inbred C57BL
• Receptors, Leukotriene B4 (metabolism)
• Skin (pathology)
• Th1 Cells (drug effects, immunology)
• Transcriptome (genetics)