Leukotriene B4—leukotriene B4 receptor axis promotes oxazolone‐induced contact dermatitis by directing skin homing of neutrophils and CD8+ T cells. Issue 1 (29th June 2015)

• Record Type: Journal Article
• Authors: Lv, Jiaoyan; Zou, Linlin; Zhao, Lina; Yang, Wei; Xiong, Yingluo; Li, Bingji; He, Rui
• Is Part Of: Immunology. Volume 146:Issue 1(2015:Sep.)
• Page Start: 50
• Page End: 58
• Publication Date: 2015-06-29
• Subjects: Immunology -- Periodicals
• DOI: 10.1111/imm.12478
• Languages: English
• ISSNs: 0019-2805

Abstract

<abstract abstract-type="main" id="imm12478-abs-0001"> <title>Summary</title> <p>Leukotriene B<sub>4</sub> (LTB<sub>4</sub>) is a lipid mediator that is rapidly generated in inflammatory sites, and its functional receptor, BLT1, 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 CD8<sup>+</sup> T cells. The role of the LTB<sub>4</sub>–BLT1 axis in contact dermatitis remains largely unknown. In this study, we found up‐regulated gene expression of 5‐lipoxygenase and leukotriene A<sub>4</sub> hydrolase, two critical enzymes for LTB<sub>4</sub> synthesis, BLT1 and elevated LTB<sub>4</sub> levels in skin lesions of oxazolone (OXA)‐induced contact dermatitis. BLT1 deficiency or blockade of LTB<sub>4</sub> and BLT1 by the antagonists, bestatin and U‐75302, respectively, in the elicitation phase caused significant decreases in ear swelling and skin‐infiltrating neutrophils and CD8<sup>+</sup> T cells, which was accompanied by significantly reduced skin expression of CXCL1, CXCL2, interferon‐<italic>γ</italic> and interleukin‐1<italic>β</italic>. Furthermore, neutrophil depletion during the elicitation phase of OXA‐induced contact dermatitis also caused significant decreases in ear swelling and CD8<sup>+</sup> T‐cell infiltration accompanied by significantly decreased LTB<sub>4</sub> synthesis and gene expression of CXCL2, interferon‐<italic>γ</italic> and interleukin‐1<italic>β</italic>. Importantly, subcutaneous injection of exogenous LTB<sub>4</sub> restored the skin infiltration of CD8<sup>+</sup> T cells in neutrophil‐depleted mice following OXA challenge. Collectively, our results demonstrate that the LTB<sub>4</sub>–BLT1 axis contributes to OXA‐induced contact dermatitis by mediating skin recruitment of neutrophils, which are a major source of LTB<sub>4</sub> that sequentially direct CD8<sup>+</sup> T‐cell homing to OXA‐challenged skin. Hence, LTB<sub>4</sub> and BLT1 could be potential therapeutic targets for the treatment of contact dermatitis.</p> </abstract>