Leukotriene B₄-leukotriene B₄ receptor axis promotes oxazolone-induced contact dermatitis by directing skin homing of neutrophils and CD8⁺ T cells.
Leukotriene B4 (LTB4 ) 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(+) T cells. The role of the LTB4 -BLT1 axis in contact dermatitis remains largely unknown. In this study, we found up-regulated gene expression of 5-lipoxygenase and leukotriene A4 hydrolase, two critical enzymes for LTB4 synthesis, BLT1 and elevated LTB4 levels in skin lesions of oxazolone (OXA)-induced contact dermatitis. BLT1 deficiency or blockade of LTB4 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(+) T cells, which was accompanied by significantly reduced skin expression of CXCL1, CXCL2, interferon-γ and interleukin-1β. Furthermore, neutrophil depletion during the elicitation phase of OXA-induced contact dermatitis also caused significant decreases in ear swelling and CD8(+) T-cell infiltration accompanied by significantly decreased LTB4 synthesis and gene expression of CXCL2, interferon-γ and interleukin-1β. Importantly, subcutaneous injection of exogenous LTB4 restored the skin infiltration of CD8(+) T cells in neutrophil-depleted mice following OXA challenge. Collectively, our results demonstrate that the LTB4 -BLT1 axis contributes to OXA-induced contact dermatitis by mediating skin recruitment of neutrophils, which are a major source of LTB4 that sequentially direct CD8(+) T-cell homing to OXA-challenged skin. Hence, LTB4 and BLT1 could be potential therapeutic targets for the treatment of contact dermatitis.
['Lv|Jiaoyan|J|', 'Zou|Linlin|L|', 'Zhao|Lina|L|', 'Yang|Wei|W|', 'Xiong|Yingluo|Y|', 'Li|Bingji|B|', 'He|Rui|R|']
D000818:Animals D001094:Arachidonate 5-Lipoxygenase D018414:CD8-Positive T-Lymphocytes D054360:Chemokine CXCL1 D054426:Chemokine CXCL2 D003877:Dermatitis, Contact D004851:Epoxide Hydrolases D005233:Fatty Alcohols D005260:Female D006018:Glycols D007249:Inflammation D007371:Interferon-gamma D053583:Interleukin-1beta D007930:Leucine D007975:Leukotriene B4 D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D009504:Neutrophils D010081:Oxazolone D018102:Receptors, Leukotriene B4 D012867:Skin
skin homing neutrophils CD8 T cells elicitation phase of contact dermatitis leukotriene B4-BLT1 axis