title: Increased plasmacytoid dendritic cells and RORγt-expressing immune effectors in cutaneous acute graft-versus-host disease.
abstract: The role of PDCs and Th17 cells is not well understood in the pathogenesis of aGVHD. We evaluated PDC and Th17 cells in skin biopsies of 38 patients at diagnosis of aGVHD. The biopsies were tested by immunohistochemistry for the expression of BDCA2, a typical marker of PDCs. We found an increase of BDCA2(+) cells in the skin of the patients with aGVHD. Moreover, we observed a strong expression of the type I IFN-inducible protein Mx1 in the skin of the patients with aGVHD, compared with that of those without it, suggesting that PDCs produce type I IFN. We also analyzed the expression of two Th17 surface markers-CD161 and CCR6-and RORγt, the key transcription factor that orchestrates the differentiation of Th17 cells. Significantly higher numbers of RORγt(+), CD161(+), and CCR6(+) cells were counted in the skin of the patients with aGVHD than in the skin of those who underwent allo-SCT and in whom aGVHD did not develop. This study provides evidence for a role of Th17-mediated responses and a potential new pathophysiological link between PDCs and Th17 in human cutaneous aGVHD.
authors.affiliation: 3.CHU Hôtel-Dieu, Université de Nantes and INSERM U892, Place Alexis Ricordeau, F-44093 Nantes, France. mohamad.mohty@inserm.fr.
authors.forename: Florent
authors.initials: F
authors.lastname: Malard
authors.forename: Céline
authors.initials: C
authors.lastname: Bossard
authors.forename: Eolia
authors.initials: E
authors.lastname: Brissot
authors.forename: Patrice
authors.initials: P
authors.lastname: Chevallier
authors.forename: Thierry
authors.initials: T
authors.lastname: Guillaume
authors.forename: Jacques
authors.initials: J
authors.lastname: Delaunay
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Mosnier
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Marc
authors.initials: M
authors.lastname: Grégoire
authors.forename: Béatrice
authors.initials: B
authors.lastname: Gaugler
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006086:Graft vs Host Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019337:Hematologic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D006801:Humans; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins / Q000096:biosynthesis / Q000276:immunology; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000096:biosynthesis / Q000276:immunology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000096:biosynthesis / Q000276:immunology*; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D054399:Receptors, CCR6 / Q000096:biosynthesis / Q000276:immunology; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology; D012871:Skin Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D033581:Stem Cell Transplantation; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: C106311:CCR6 protein, human; C443299:CLEC4C protein, human; D007370:Interferon Type I; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; C579071:MX1 protein, human; D008562:Membrane Glycoproteins; D064547:Myxovirus Resistance Proteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D054399:Receptors, CCR6; D011971:Receptors, Immunologic
keywords: Th17 cells; Type I Interferon; allogeneic stem cell transplantation