Leukotriene B4-driven neutrophil recruitment to the skin is essential for allergic skin inflammation.
Scratching triggers skin flares in atopic dermatitis. We demonstrate that scratching of human skin and tape stripping of mouse skin cause neutrophil influx. In mice, this influx was largely dependent on the generation of leukotriene B4 (LTB4) by neutrophils and their expression of the LTB4 receptor BLT1. Allergic skin inflammation in response to epicutaneous (EC) application of ovalbumin to tape-stripped skin was severely impaired in Ltb4r1(-/-) mice and required expression of BLT1 on both T cells and non-T cells. Cotransfer of wild-type (WT) neutrophils, but not neutrophils deficient in BLT1 or the LTB4-synthesizing enzyme LTA4H, restored the ability of WT CD4(+) effector T cells to transfer allergic skin inflammation to Ltb4r1(-/-) recipients. Pharmacologic blockade of LTB4 synthesis inhibited allergic skin inflammation elicited by cutaneous antigen challenge in previously EC-sensitized mice. Our results demonstrate that a neutrophil-T cell axis reliant on LTB4-BLT1 interaction is required for allergic skin inflammation.
Division of Immunology, Boston Children's Hospital, MA 02115, USA. michiko.oyoshi@childrens.harvard.edu
Michiko K
MK
Oyoshi
Rui
R
He
Yitang
Y
Li
Subhanjan
S
Mondal
Juhan
J
Yoon
Roshi
R
Afshar
Mei
M
Chen
David M
DM
Lee
Hongbo R
HR
Luo
Andrew D
AD
Luster
John S
JS
Cho
Lloyd S
LS
Miller
Allison
A
Larson
George F
GF
Murphy
Raif S
RS
Geha
D000818:Animals; D001706:Biopsy; D003872:Dermatitis / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007975:Leukotriene B4 / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology*; D018102:Receptors, Leukotriene B4 / Q000172:deficiency / Q000276:immunology
C513240:LTB4R protein, human; C503704:Ltb4r1 protein, mouse; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4