title: Regulation of Langerhans cell functions in a hypoxic environment.
abstract: Langerhans cells (LCs) are a specialized dendritic cell subset that resides in the epidermis and mucosal epithelia and is critical for the orchestration of skin immunity. Recent evidence suggest that LCs are involved in aberrant wound healing and in the development of hypertrophic scars and chronic wounds, which are characterized by a hypoxic environment. Understanding LCs biology under hypoxia may, thus, lead to the identification of novel pathogenetic mechanisms of wound repair disorders and open new therapeutic opportunities to improve wound healing. In this study, we characterize a previously unrecognized role for hypoxia in significantly affecting the phenotype and functional properties of human monocyte-derived LCs, impairing their ability to stimulate naive T cell responses, and identify the triggering receptor expressed on myeloid (TREM)-1, a member of the Ig immunoregulatory receptor family, as a new hypoxia-inducible gene in LCs and an activator of their proinflammatory and Th1-polarizing functions in a hypoxic environment. Furthermore, we provide the first evidence of TREM-1 expression in vivo in LCs infiltrating hypoxic areas of active hypertrophic scars and decubitous ulcers, pointing to a potential pathogenic role of this molecule in wound repair disorders.
  
  
  
  Hypoxia modulates surface molecule expression and cytokine profile in Langerhans cells. Hypoxia impairs human Langerhans cell stimulatory activity on naive T cells. Hypoxia selectively induces TREM-1 expression in human Langerhans cells. TREM-1 engagement stimulates Langerhans cell inflammatory and Th1-polarizing activity. TREM-1 is expressed in vivo in Langerhans cells infiltrating hypoxic skin lesions.
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.|CERMS, AOU Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Pierobon
authors.affiliation: Laboratory of Molecular Biology, G.Gaslini Institute, Genova, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Raggi
authors.affiliation: Department of Reconstructive Plastic Surgery, Burns Centre and Skin Bank, Trauma Center, Torino, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Cambieri
authors.affiliation: Laboratory of Molecular Biology, G.Gaslini Institute, Genova, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Pelassa
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.|CERMS, AOU Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Occhipinti
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.|CERMS, AOU Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cappello
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.|CERMS, AOU Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Novelli
authors.affiliation: Department of Public Health and Pediatric Sciences, University of Torino, Torino, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Musso
authors.affiliation: Laboratory of Molecular Biology, G.Gaslini Institute, Genova, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Eva
authors.affiliation: Department of Reconstructive Plastic Surgery, Burns Centre and Skin Bank, Trauma Center, Torino, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Castagnoli
authors.affiliation: Laboratory of Molecular Biology, G.Gaslini Institute, Genova, Italy. luigivaresio@gaslini.org.|Laboratorio di Biologia Molecolare, Istituto Giannina Gaslini, Padiglione 2, L.go G.Gaslini 5, 16147, Genova Quarto, Italy. luigivaresio@gaslini.org.
authors.forename: Luigi
authors.initials: L
authors.lastname: Varesio
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.|CERMS, AOU Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Giovarelli
authors.affiliation: Laboratory of Molecular Biology, G.Gaslini Institute, Genova, Italy. mariacarlabosco@gasini.org.|Laboratorio di Biologia Molecolare, Istituto Giannina Gaslini, Padiglione 2, L.go G.Gaslini 5, 16147, Genova Quarto, Italy. mariacarlabosco@gasini.org.
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Bosco
mesh_terms: D015687:Cell Hypoxia; D049109:Cell Proliferation; D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007801:Langerhans Cells / Q000502:physiology*; D008213:Lymphocyte Activation; D012867:Skin / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000502:physiology; D000073871:Triggering Receptor Expressed on Myeloid Cells-1 / Q000378:metabolism
chemical_list: D016207:Cytokines; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
keywords: Hypoxia; Immunoregulatory receptors; Langerhans cells; Wounds