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

Abstract

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.

• Authors: Takashi Hashimoto, Takahiro Satoh, Hiroo Yokozeki
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 194 Issue 10 Pg. 4631-40 (May 15 2015) ISSN: 1550-6606 [Electronic] United States
• PMID: 25862819 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 by The American Association of Immunologists, Inc.

Chemical References

• RNA, Small Interfering
• STAT6 Transcription Factor
• Stat6 protein, mouse

Topics

• Animals
• Basophils (immunology)
• Disease Models, Animal
• Flow Cytometry
• Hypersensitivity (immunology)
• Immunohistochemistry
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Transgenic
• Prurigo (immunology)
• RNA, Small Interfering
• Real-Time Polymerase Chain Reaction
• STAT6 Transcription Factor (immunology)
• Th2 Cells (immunology)
• Transfection