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

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, BLT1^hi and BLT1^lo DCs. We also found that BLT1^hi and BLT1^lo 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 BLT1^hi DCs exacerbated allergic contact dermatitis. Comprehensive transcriptome analysis revealed that BLT1^hi DCs preferentially induced Th1 differentiation by upregulating IL-12p35 expression, whereas BLT1^lo 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.