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- Title
Activin A Induces Langerhans Cell Differentiation In Vitro and in Human Skin Explants.
- Authors
Musso, Tiziana; Scutera, Sara; Vermi, William; Daniele, Roberta; Fornaro, Michele; Castagnoli, Carlotta; Alotto, Daniela; Ravanini, Maria; Cambieri, Irene; Salogni, Laura; Elia, Angela Rita; Giovarelli, Mirella; Facchetti, Fabio; Girolomoni, Giampiero; Sozzani, Silvano
- Abstract
Langerhans cells (LC) represent a well characterized subset of dendritic cells located in the epidermis of skin and mucosae. In vivo, they originate from resident and blood-borne precursors in the presence of keratinocyte-derived TGFb. In vitro, LC can be generated from monocytes in the presence of GM-CSF, IL-4 and TGFb. However, the signals that induce LC during an inflammatory reaction are not fully investigated. Here we report that Activin A, a TGFb family member induced by proinflammatory cytokines and involved in skin morphogenesis and wound healing, induces the differentiation of human monocytes into LC in the absence of TGFb. Activin A-induced LC are Langerin+, Birbeck granules+, E-cadherin+, CLA+ and CCR6+ and possess typical APC functions. In human skin explants, intradermal injection of Activin A increased the number of CD1a+ and Langerin+ cells in both the epidermis and dermis by promoting the differentiation of resident precursor cells. High levels of Activin A were present in the upper epidermal layers and in the dermis of Lichen Planus biopsies in association with a marked infiltration of CD1a+ and Langerin+ cells. This study reports that Activin A induces the differentiation of circulating CD14+ cells into LC. Since Activin A is abundantly produced during inflammatory conditions which are also characterized by increased numbers of LC, we propose that this cytokine represents a new pathway, alternative to TGFb, responsible for LC differentiation during inflammatory/autoimmune conditions.
- Subjects
ACTIVIN; LANGERHANS cells; EPIDERMIS; DENDRITIC cells; KERATINOCYTES; MONOCYTES; CYTOKINES; INTRADERMAL injections; MORPHOGENESIS
- Publication
PLoS ONE, 2008, Vol 3, Issue 9, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0003271