Leukotriene B 4 —leukotriene B 4 receptor axis promotes oxazolone‐induced contact dermatitis by directing skin homing of neutrophils and CD 8 + T cells

Summary Leukotriene B 4 ( LTB 4 ) is a lipid mediator that is rapidly generated in inflammatory sites, and its functional receptor, BLT 1, is mostly expressed on immune cells. Contact dermatitis is a common inflammatory skin disease characterized by skin oedema and abundant inflammatory infiltrates, primarily including neutrophils and CD 8 + T cells. The role of the LTB 4 – BLT 1 axis in contact dermatitis remains largely unknown. In this study, we found up‐regulated gene expression of 5‐lipoxygenase and leukotriene A 4 hydrolase, two critical enzymes for LTB 4 synthesis, BLT 1 and elevated LTB 4 levels in skin lesions of oxazolone ( OXA )‐induced contact dermatitis. BLT 1 deficiency or blockade of LTB 4 and BLT 1 by the antagonists, bestatin and U‐75302, respectively, in the elicitation phase caused significant decreases in ear swelling and skin‐infiltrating neutrophils and CD 8 + T cells, which was accompanied by significantly reduced skin expression of CXCL 1, CXCL 2, interferon‐ γ and interleukin‐1 β . Furthermore, neutrophil depletion during the elicitation phase of OXA ‐induced contact dermatitis also caused significant decreases in ear swelling and CD 8 + T‐cell infiltration accompanied by significantly decreased LTB 4 synthesis and gene expression of CXCL 2, interferon‐ γ and interleukin‐1 β . Importantly, subcutaneous injection of exogenous LTB 4 restored the skin infiltration of CD 8 + T cells in neutrophil‐depleted mice following OXA challenge. Collectively, our results demonstrate that the LTB 4 – BLT 1 axis contributes to OXA ‐induced contact dermatitis by mediating skin recruitment of neutrophils, which are a major source of LTB 4 that sequentially direct CD 8 + T‐cell homing to OXA ‐challenged skin. Hence, LTB 4 and BLT 1 could be potential therapeutic targets for the treatment of contact dermatitis.