Development of atopic dermatitis-like skin lesions in STAT6-deficient NC/Nga mice.
Atopic dermatitis (AD) is a pruritic inflammatory skin disease characterized by elevation of plasma levels of total IgE, infiltration of mast cells and eosinophils, and the expression of cytokines by Th2 T cells. However, the role of Th2 cells in the pathogenesis of AD is not fully understood. In this study we examined the NC/Nga (NC) mouse model of AD and established STAT6-deficient (SATA6(-/-)) NC mice to investigate the relevance of IL-4-mediated immune responses. Surprisingly, these mice elicited AD-like skin lesions at equivalent frequency and time of onset compared with normal NC littermates. Histological features of the lesion in STAT6(-/-) NC mice fulfilled the criteria for the pathogenesis of AD, although these mice fail to produce IgE and Th2 cytokines. The lymph nodes proximal to the regions of skin that developed lesions exhibited massive enlargement elicited by the accumulation of activated IFN-gamma-secreting T cells. Moreover, caspase I, IL-18, IL-12, and IFN-gamma are found to be highly expressed at the skin lesion, occurring simultaneously with elevation of eotaxin 2 and CCR3 expression. Therefore, the Th2-mediated immune response is not necessary for the development of AD-like skin disease in NC mice. The skin microenvironment that favored IFN-gamma production tightly correlates with the skin disease in NC mice through the infiltration of eosinophils.
Yagi
Ryouji
R
Division of Immunobiology, Research Institute for Biological Sciences, Department of Applied Biological Science, Science University of Tokyo, Noda City, Chiba, Japan.
Nagai
Haruko
H
Iigo
Yutaka
Y
Akimoto
Toshihiro
T
Arai
Takao
T
Kubo
Masato
M
D000818:Animals; D000906:Antibodies / Q000097:blood; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003876:Dermatitis, Atopic / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics; D050800:STAT6 Transcription Factor; D012867:Skin / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology*
D000906:Antibodies; D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D007073:Immunoglobulin E