Author

Erin Foster

Date

August 2010

Document Type

Dissertation

Degree Name

Ph.D.

Department

Dept. of Molecular Microbiology and Immunology

Institution

Oregon Health & Science University

Abstract

Cutaneous nerves are increased in atopic dermatitis, and itch is a prominent symptom. The functional interactions between eosinophils and nerves were studied in human and mouse skin and in culture. Human atopic dermatitis skin has eosinophil granule proteins present in the same region as increased nerves. Epicutaneous sensitization of wild-type mice, but not mice deficient in eosinophils, increased cutaneous nerves predominantly in the papillary dermis. Transgenic mice in which interleukin-5 (IL-5) expression is driven by a keratin-14 (K14) promoter had eosinophil proteins in the epidermis, and the number of nerves was also significantly increased in the epidermis. Mice lacking filaggrin, which are a model for atopic dermatitis, also had increased nerves in skin, as did keratin-5-TGF -1 transgenic mice, which have high IgE levels and eosinophils in the dermis. In cocultures, eosinophils dramatically increased branching of sensory neurons isolated from the dorsal root ganglia (DRG) of mice. This effect did not occur in DRG neurons co-cultured with mast cells or with dead eosinophils. Physical contact of the eosinophils with the neurons was not required, and the effect was not blocked by an antibody to nerve growth factor. DRG neurons recruit and bind eosinophils in vitro and synthesize eotaxin-1 and ICAM-1 and VCAM-1. These data indicate a new therapeutic target in atopic dermatitis and other eosinophilic skin conditions with neuronal symptoms such as itch.

Identifier

doi:10.6083/M4C53HVH

School

School of Medicine

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