Roles of TH1 and TH2 cytokines in a murine model of allergic dermatitis

Spergel, Jonathan M.; Mizoguchi, Emiko; Oettgen, Hans C.; Bhan, Atul K.; Geha, Raif S.

doi:10.1172/jci5669

Cited by 364 publications

(310 citation statements)

References 50 publications

(52 reference statements)

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“…These findings agree with previous reports that the Ag sensitization elicited the AD-like skin lesions in IgE-deficient mice (29). The thickening of the skin layer in the lesions at the OVA-sensitized site of IgE-deficient mice was similar to the skin lesions in STAT6-deficient NC mice.…”

Section: Discussionsupporting

confidence: 92%

“…The infiltration of eosinophils and mast cells in STAT6-deficient NC mice was elicited in the absence of IL-4-and IL-5-producing T cells. However, this Ag-sensitized mouse model indicates the functional significance of IL-4 and IL-5 in the infiltration of eosinophils (29). These results indicate that the mechanisms regulating skin disease in NC mice differ from the Ag sensitization elicited by the AD-like skin lesions.…”

Section: Discussionmentioning

confidence: 66%

“…role in allergic eczema formation (29,31). Moreover, recent reports demonstrated that transgenic mice expressing caspase 1 in keratinocytes spontaneously developed AD-like skin disease with an elevation of the active form of IL-18 in serum (37).…”

Section: Discussionmentioning

confidence: 99%

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Development of Atopic Dermatitis-Like Skin Lesions in STAT6-Deficient NC/Nga Mice

Yagi

Nagai

Iigo

et al. 2002

The Journal of Immunology

122

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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-γ-secreting T cells. Moreover, caspase I, IL-18, IL-12, and IFN-γ 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-γ production tightly correlates with the skin disease in NC mice through the infiltration of eosinophils.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 66%

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Development of Atopic Dermatitis-Like Skin Lesions in STAT6-Deficient NC/Nga Mice

Yagi

Nagai

Iigo

et al. 2002

The Journal of Immunology

122

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“…6,7 In addition, the expression of not only Th2-type cytokine but also Th1-type cytokine (ie, IFN-␥ or IL-12) played a critical role in murine dermatitis and asthma models. 8,9 It has also been demonstrated that natural killer (NK) cells, like Th2 cells, play an important role in the development of allergen-induced asthma. 9 It has been suggested that antigen-presenting cells (APCs) play a crucial role in the skewing of Th1 and Th2 differentiation.…”

mentioning

confidence: 99%

Pathological Role of Large Intestinal IL-12p40 for the Induction of Th2-Type Allergic Diarrhea

Hino

Kweon

Fujihashi

et al. 2004

The American Journal of Pathology

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IL-12 consists of two disulfide-linked subunits, p40 and p35, that form functionally active heterodimers for the induction of Th1 cells. In contrast to IL-12 heterodimers, p40 monomers and homodimers possess inhibitory effects on Th1 cells leading to the creation of a Th2 environment. Although it has been shown that IL-12p40 acts as antagonist of IL-12p70 in vitro, no evidence is currently available whether IL-12p40 is functional in vivo. We now report that IL12p40 plays an important pathological role in an intestinal allergic disease. A high expression of IL12p40 protein was demonstrated in epithelial cells, dendritic cells, and macrophages in large but not small intestine of allergic diarrhea-induced mice. Interestingly, neutralization with anti-IL-12p40 mAbs reduced the incidence and delayed the onset of disease development. Lower levels of ovalbumin (OVA)-specific IgE Abs in serum were detected in anti-IL12p40 mAb-treated mice than in control Ab-treated mice. The secretion of Th2 cytokines and eotaxin by the mononuclear cells isolated from the large intestine of anti-IL-12p40 mAb-treated mice was significantly decreased. Finally, the removal of the IL-12p40 gene resulted in complete inhibition of disease development. These results show that over-expression of IL-12p40 is an important contributing factor for the generation of the dominant Th2-type environment in the large intestine of mice with allergic diarrhea.

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“…76 On the contrary, allergen sensitized skin from mice deficient in IL-4 and IL-5 lack eosinophils and the skin from IFN-γ-deficient mice demonstrate decreased thickening of the dermis indicating the importance of Th1 and Th2 cytokines in AD. 77 Other studies have indicated the importance of Th2-cytokines, IL-4 and IL-13 at the onset of AD and IL-5 at the later stages of AD. 74 In addition to the Th1 and Th2 subset of T cells, defects in T regulatory cells have been implicated in the development of polyendocrinopathy X-linked syndrome involving hyper-IgE, food allergy, and eczema.…”

Section: Immune Mechanisms In Atopic Dermatitis a Effector Cells T Cmentioning

confidence: 98%

Clinical correlations of recent developments in the pathogenesis of atopic dermatitis

Sehra

Tuana

Holbreich

et al. 2008

An. Bras. Dermatol.

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Atopic dermatitis is a chronic inflammatory skin disease with a steadily increasing prevalence affecting 10-20 % of infants and 1-3% of adults globally. It is often the first clinical manifestation of atopic disease preceding asthma and allergic rhinitis. Probably half of the children with atopic dermatitis develop some other form of atopic disease later in life. The pathogenesis involves a complex interplay of factors including genetic predisposition due to altered immune or skin barrier function, interactions with the environment such as food and allergen exposures, and infectious triggers of inflammation. In this review, we summarize the recent advances in understanding the contribution of different factors in the pathophysiology of atopic dermatitis and how insights provide new therapeutic potential for its treatment. Keywords: Asthma; Atopic Dermatitis, Eczema; Eosinophils; Genetics; Immunoglobulin E; Keratinocytes; Rhinitis, T-Lymphocytes Resumo: A dermatite atópica é uma doença cutânea inflamatória crônica cuja prevalência tem aumentado de forma constante, afetando 10-20% dos lactentes e 1-3% dos adultos em todo o mundo. Ela é freqüentemente a primeira manifestação clínica de doença atópica, precedendo a asma e a rinite alérgica. Provavelmente metade das crianças com dermatite atópica desenvolvem alguma

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Roles of TH1 and TH2 cytokines in a murine model of allergic dermatitis

Cited by 364 publications

References 50 publications

Development of Atopic Dermatitis-Like Skin Lesions in STAT6-Deficient NC/Nga Mice

Development of Atopic Dermatitis-Like Skin Lesions in STAT6-Deficient NC/Nga Mice

Pathological Role of Large Intestinal IL-12p40 for the Induction of Th2-Type Allergic Diarrhea

Clinical correlations of recent developments in the pathogenesis of atopic dermatitis

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