title: Eosinophils increase neuron branching in human and murine skin and in vitro.
abstract: Cutaneous nerves are increased in atopic dermatitis, and itch is a prominent symptom. We studied the functional interactions between eosinophils and nerves in human and mouse skin and in culture. We demonstrated that human atopic dermatitis skin has eosinophil granule proteins present in the same region as increased nerves. Transgenic mice in which interleukin-5 (IL-5) expression is driven by a keratin-14 (K14) promoter had many eosinophils in the epidermis, and the number of nerves was also significantly increased in the epidermis. In co-cultures, 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 express eotaxin-1, ICAM-1 and VCAM-1, which may be important in the recruitment, binding, and activation of eosinophils in the region of cutaneous nerves. These data indicate a pathophysiological role for eosinophils in cutaneous nerve growth in atopic dermatitis, and suggest they may present a therapeutic target in atopic dermatitis and other eosinophilic skin conditions with neuronal symptoms such as itch.
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Foster
authors.forename: Eric L
authors.initials: EL
authors.lastname: Simpson
authors.forename: Lorna J
authors.initials: LJ
authors.lastname: Fredrikson
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Lee
authors.forename: Allison D
authors.initials: AD
authors.lastname: Fryer
authors.forename: David B
authors.initials: DB
authors.lastname: Jacoby
mesh_terms: D000818:Animals; D001706:Biopsy; D002450:Cell Communication; D002452:Cell Count; D002470:Cell Survival; D054413:Chemokine CCL11 / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology / Q000473:pathology; D020405:Dermis / Q000276:immunology / Q000294:innervation / Q000473:pathology; D047091:Eosinophil Granule Proteins / Q000378:metabolism; D047209:Eosinophil Peroxidase / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology / Q000276:immunology*; D004817:Epidermis / Q000276:immunology / Q000294:innervation / Q000473:pathology; D005727:Ganglia, Spinal / Q000378:metabolism; D006262:Health; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D016501:Neurites / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000276:immunology / Q000378:metabolism*; D012867:Skin / Q000201:enzymology / Q000276:immunology* / Q000294:innervation* / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D054413:Chemokine CCL11; D047091:Eosinophil Granule Proteins; D015848:Interleukin-5; D009414:Nerve Growth Factors; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D047209:Eosinophil Peroxidase