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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.
Highlights
Dendritic cells (DCs) are specialized antigen-presenting cells that reside at host-environment boundaries, such as the skin, lungs, and intestine
Identification of B4 (LTB4) receptor 1 (BLT1)-positive and BLT1-negative DC subsets To examine the role of BLT1 in DCs, we first analyzed the expression of BLT1 at the protein level
Cells showing one of these expression profiles were observed in the BMDC and lung DC populations (Fig. 1c, f); no BLT1-expressing DCs were detected in the lymph nodes (Fig. 1g)
Summary
Dendritic cells (DCs) are specialized antigen-presenting cells that reside at host-environment boundaries, such as the skin, lungs, and intestine. DCs capture antigens in the periphery and migrate toward draining lymph nodes. Migrated DCs activate naïve T cells by presenting antigen-loaded MHC class II molecules and by producing cytokines that induce T cell differentiation (i.e., interleukin [IL]-12 for Th1 cells; IL-4 for Th2 cells; IL-6, IL-23, and transforming growth factor [TGF]-β for Th17 cells; and TGF-β for regulatory T cells [Tregs]). DCs are a crucial “control tower” for acquired immune responses. Recent reports show that in addition to migrating to lymph nodes, DCs migrate toward peripheral inflammatory areas to form DC-T cell clusters; both pathways are important for efficient antigen presentation and T cell expansion.[1,2,3,4] the migratory and cytokine-producing abilities of DCs are crucial for efficient control of acquired immune responses
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