Activin A induces Langerhans cell differentiation in vitro and in human skin explants.
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 TGFbeta. In vitro, LC can be generated from monocytes in the presence of GM-CSF, IL-4 and TGFbeta. However, the signals that induce LC during an inflammatory reaction are not fully investigated. Here we report that Activin A, a TGFbeta family member induced by pro-inflammatory cytokines and involved in skin morphogenesis and wound healing, induces the differentiation of human monocytes into LC in the absence of TGFbeta. 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 TGFbeta, responsible for LC differentiation during inflammatory/autoimmune conditions.
Musso
Tiziana
T
Department of Public Health and Microbiology, University of Torino, Turin, Italy.
Scutera
Sara
S
Vermi
William
W
Daniele
Roberta
R
Fornaro
Michele
M
Castagnoli
Carlotta
C
Alotto
Daniela
D
Ravanini
Maria
M
Cambieri
Irene
I
Salogni
Laura
L
Elia
Angela Rita
AR
Giovarelli
Mirella
M
Facchetti
Fabio
F
Girolomoni
Giampiero
G
Sozzani
Silvano
S
D028341:Activins / Q000378:metabolism*; D015703:Antigens, CD / Q000096:biosynthesis; D018949:Antigens, CD1 / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology; D006801:Humans; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000166:cytology; D007801:Langerhans Cells / Q000166:cytology*; D037181:Lectins, C-Type / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D037241:Mannose-Binding Lectins / Q000096:biosynthesis; D008954:Models, Biological; D009000:Monocytes / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014945:Wound Healing
D015703:Antigens, CD; D018949:Antigens, CD1; C419393:CD1a antigen; C121916:CD207 protein, human; D037181:Lectins, C-Type; D018950:Lipopolysaccharide Receptors; D037241:Mannose-Binding Lectins; D016212:Transforming Growth Factor beta; C422405:activin A; D028341:Activins