Basophils regulate the recruitment of eosinophils in a murine model of irritant contact dermatitis.
BACKGROUND
Although eosinophils have been detected in several human skin diseases in the vicinity of basophils, how eosinophils infiltrate the skin and the role of eosinophils in the development of skin inflammation have yet to be examined.


OBJECTIVE
Using murine irritant contact dermatitis (ICD) as a model, we sought to clarify the roles of eosinophils in ICD and the underlying mechanism of eosinophil infiltration of the skin.


METHODS
We induced croton oil-induced ICD in eosinophil-deficient ΔdblGATA mice with or without a reactive oxygen species (ROS) inhibitor. We performed cocultivation with fibroblasts and bone marrow-derived basophils and evaluated eosinophil migration using a chemotaxis assay.


RESULTS
ICD responses were significantly attenuated in the absence of eosinophils or by treatment with the ROS inhibitor. ROS was produced abundantly by eosinophils, and both basophils and eosinophils were detected in human and murine ICD skin lesions. In coculture experiments, basophils attracted eosinophils, especially in the presence of fibroblasts. Moreover, basophils produced IL-4 and TNF-α in contact with fibroblasts and promoted the expression of eotaxin/CCL11 from fibroblasts in vitro.


CONCLUSIONS
Eosinophils mediated the development of murine ICD, possibly through ROS production. Recruitment of eosinophils into the skin was induced by basophils in cooperation with fibroblasts. Our findings introduce the novel concept that basophils promote the recruitment of eosinophils into the skin through fibroblasts in the development of skin inflammation.
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Chisa
C
Nakashima
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: otsukamn@kuhp.kyoto-u.ac.jp.
Atsushi
A
Otsuka
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Akihiko
A
Kitoh
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Tetsuya
T
Honda
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Gyohei
G
Egawa
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Saeko
S
Nakajima
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Satoshi
S
Nakamizo
Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
Makoto
M
Arita
Laboratory for Cytokine Regulation, Integrative Medical Science (IMS), RIKEN Yokohama Institute, Kanagawa, Japan; Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science, Chiba, Japan.
Masato
M
Kubo
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Yoshiki
Y
Miyachi
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: kaba@kuhp.kyoto-u.ac.jp.
Kenji
K
Kabashima
D000818:Animals; D001491:Basophils / Q000276:immunology* / Q000473:pathology; D002450:Cell Communication; D054413:Chemokine CCL11 / Q000235:genetics / Q000276:immunology; D002633:Chemotaxis; D018920:Coculture Techniques; D003436:Croton Oil; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D005347:Fibroblasts / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D007509:Irritants; D051379:Mice; D018345:Mice, Knockout; D017382:Reactive Oxygen Species / Q000276:immunology; D015398:Signal Transduction; D012867:Skin / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; C556062:IL10 protein, mouse; D007509:Irritants; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D003436:Croton Oil
Eosinophil; RANTES/CCL5; basophil; eotaxin/CCL11; fibroblast; irritant contact dermatitis; reactive oxygen species; tumor necrosis factor