title: Activin a inhibits antigen-induced allergy in murine epicutaneous sensitization.
abstract: Activin A, a member of the TGFβ superfamily, is involved in physiological processes such as cell differentiation, tissue homeostasis, wound healing, reproduction, and in pathological conditions, such as fibrosis, cancer, and asthma. Activin enhances mast cell maturation, as well as regulatory T-cell and Langerhans cell differentiation. In this study we investigated the potential role of activin in epicutaneous sensitization with ovalbumin (OVA), notably with respect to its effect on known Th2-polarization. For this purpose, transgenic mice overexpressing activin in keratinocytes and their wild-type (WT) controls were sensitized epicutaneously with OVA. Skin biopsies were analyzed with regard to histopathological features and mRNA expression of pro-inflammatory and Th1/Th2 cytokines, and Ig levels were measured in the serum. Unexpectedly, activin overexpressing animals were protected from Th2-cytokine expression and induction of OVA-specific IgE levels compared to WT animals. On the other hand, transgenic mice were more susceptible to inflammation compared to WT littermates after tape-stripping and saline (vehicle) or OVA application, as shown by increased pro-inflammatory cytokine mRNA levels and neutrophil accumulation at the site of the treatment. We conclude that activin protects from antigen-induced cutaneous Th2-polarization through modulation of the immune response. These findings highlight the role of activin in cutaneous sensitization, allergy, and in skin homeostasis.
authors.affiliation: Laboratory of Cutaneous Biology, Service of Dermatology and Venereology, Beaumont Hospital, CHUV , Lausanne , Switzerland.
authors.forename: Magdalini
authors.initials: M
authors.lastname: Kypriotou
authors.forename: Dianelys
authors.initials: D
authors.lastname: Rivero
authors.forename: Sergio
authors.initials: S
authors.lastname: Haller
authors.forename: Anita
authors.initials: A
authors.lastname: Mariotto
authors.forename: Marcel
authors.initials: M
authors.lastname: Huber
authors.forename: Hans
authors.initials: H
authors.lastname: Acha-Orbea
authors.forename: Sabine
authors.initials: S
authors.lastname: Werner
authors.forename: Daniel
authors.initials: D
authors.lastname: Hohl
keywords: activin; atopy; epicutaneous sensitization; inflammation; transgenic mice