Nuclear localization of activated STAT6 and STAT3 in epidermis of prurigo nodularis

Fukushi, Sawako; Yamasaki, Kenshi; Aiba, Setsuya

doi:10.1111/j.1365-2133.2011.10498.x

Cited by 96 publications

(92 citation statements)

References 28 publications

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“…Substantial numbers of basophils also were observed in the dermis and occasionally in the epidermis, as detected by a basophil-specific Ab (TUG8) (25). Epidermal keratinocytes and the dermal cells showed nuclear translocation of phospho-STAT6 and phospho-STAT3; these results agreed with a recent report indicating that human prurigo lesions exhibit activation of the same transcription factors (32).…”

Section: Repeated Induction Of the Ige-vlpr Results In Formation Of Psupporting

confidence: 82%

Protective Role of STAT6 in Basophil-Dependent Prurigo-like Allergic Skin Inflammation

Hashimoto

Satoh

Yokozeki

2015

The Journal of Immunology

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Prurigo is a common, but treatment-resistant, skin disease characterized by persistent papules/nodules and severe itching. Prurigo occurs in association with various underlying diseases, such as diabetes, chronic renal failure, and internal malignancies. Atopic dermatitis is occasionally complicated by prurigo lesions. However, the pathology of prurigo is completely undefined. We demonstrate that repeated intradermal administration of Ag to IgE-transgenic mice causes persistent and pruritic papulonodular skin lesions mimicking prurigo. Skin lesions were histopathologically characterized by irregular acanthosis and dermal cellular infiltrates comprising eosinophils, mononuclear cells, and basophils, with epidermal nerve fiber sprouting. In vivo depletion of basophils alleviated skin reactions, indicating that the inflammation is basophil dependent. Unexpectedly, STAT6 signaling was unnecessary for skin lesion development if IgE was present. Moreover, the absence of STAT6 signaling exacerbated the inflammation, apparently as the result of impaired generation of an M2-type anti-inflammatory macrophage response. These results provide novel insights into the pathologic mechanisms underlying prurigo. Although basophils are indispensable for prurigo-like inflammation, Th2 immunity mediated by STAT6 appears to play a protective role, and therapies targeting Th2-type cytokines may risk aggravating the inflammation.

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Section: Repeated Induction Of the Ige-vlpr Results In Formation Of Psupporting

confidence: 82%

Protective Role of STAT6 in Basophil-Dependent Prurigo-like Allergic Skin Inflammation

Hashimoto

Satoh

Yokozeki

2015

The Journal of Immunology

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“…To confirm the immunological difference between KA and SCC, we investigated further the cytokine profiles, focusing on Thl cytokines as we previously reported (21,22). Although we detected increased numbers of interferon (IFN)-y producing cells in both KA and SCC (data not shown), the increased numbers of IL-27-producing cells were observed only in KA (Fig.…”

Section: Expression Of Il-2 7 and Phosphorylated Signal Transducer Anmentioning

confidence: 48%

Comparison of Immunosuppressive and Immunomodulatory Cells in Keratoacanthoma and Cutaneous Squamous Cell Carcinoma

Kambayashi¹,

Fujimura²,

Aiba³

2013

Acta Derm Venerol

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An imbalance of immunosuppressive and immunomodulatory cells plays an important role in inhibiting the anti-tumour immune response in a tumour-bearing host. Among such cells, regulatory T cells (Tregs), together with immunosuppressive macrophages, such as CD163+ M2 macrophages, play roles in maintaining the tumour microenvironment. In contrast, interleukin-27 (IL-27) induces STAT1 and STAT3 activation, thus resulting in the enhancement of naive CD4 T-cell proliferation, the promotion of early Th1 differentiation, and the induction of the anti-tumour immune response. The purpose of this study was to investigate the involvement of immunosuppressive cells, such as Tregs and CD163+ macrophages, as well as immunomodulatory cells (i.e. IL-27-producing cells) in keratoacanthoma (KA) and invasive squamous cell carcinoma (SCC). We also examined the presence of CD3+ Foxp3+ Tregs cells in lesional skin from 10 patients with KA and 18 patients with SCC. Increased numbers of CD3+ Foxp3+ Tregs were observed in SCC compared with KA. In parallel with Tregs, higher numbers of CD163+ macrophages and MMP-9+ cells were detected only in SCC. In contrast, IL-27-producing cells were increased only in KA. In addition, the expression of pSTAT1 on tumour cells was observed only in KA. These findings suggest that the induction of immunosuppressive and immunomodulatory cells differs between KA and SCC.

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“…How VEGF might contribute to severe pruritus is currently unknown. It has been postulated that activation of STAT6 by Th2 cytokines and STAT3 by utiknown stimuli in the skin of patients is responsible for prurigo symptoms (3). Interestingly, VEGF is a known activator of STAT3 (15) and could therefore represent this unknown factor.…”

Section: Discussionmentioning

confidence: 99%

Effective Control of Recalcitrant Pruritus by Bevacizumab: A Possible Role for Vascular Endothelial Growth Factor in Chronic Itch?

Krause¹,

Krull²,

Kessler³

et al. 2013

Acta Derm Venerol

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Prurigo is a difficult to treat condition characterized by severe pruritus presenting with chronic secondary scratch lesions. We report here a dramatic improvement in pruritus in a patient with prurigo simplex who was being treated with bevacizumab, a monoclonal vascular endothelial growth factor (VEGF) antibody. On the basis of the increased VEGF expression measured in the skin of this patient, serum levels of VEGF were subsequently analysed in 27 consecutive patients with prurigo and 19 healthy controls. VEGF levels were significantly increased in the serum of patients with prurigo. Moreover, VEGF concentrations correlated with physician-assessed disease activity. Based on these observations, we speculate that VEGF is involved in the pathophysiology of prurigo.

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Nuclear localization of activated STAT6 and STAT3 in epidermis of prurigo nodularis

Abstract: These data indicated that Th2 cytokines related to STAT6 activation together with some unknown stimuli that activate STAT3 play a principal role in the pathogenesis of PN.

Cited by 96 publications

References 28 publications

Protective Role of STAT6 in Basophil-Dependent Prurigo-like Allergic Skin Inflammation

Protective Role of STAT6 in Basophil-Dependent Prurigo-like Allergic Skin Inflammation

Comparison of Immunosuppressive and Immunomodulatory Cells in Keratoacanthoma and Cutaneous Squamous Cell Carcinoma

Effective Control of Recalcitrant Pruritus by Bevacizumab: A Possible Role for Vascular Endothelial Growth Factor in Chronic Itch?

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