title: Plasmacytoid dendritic cells and Th17 immune response contribution in gastrointestinal acute graft-versus-host disease.
abstract: The contribution of Th17 cells in acute graft-versus-host disease (aGVHD) has been demonstrated in aGVHD mouse models. However, their contribution in human gastrointestinal aGVHD remains unclear. We evaluated Th17 cells in a cohort of 23 patients at diagnosis of aGVHD. In this study, we have shown that the absolute number of Th17 cells using the CCR6 and CD161 markers were significantly higher in the intestinal mucosa of patients with aGVHD compared with intestinal mucosa of patients without aGVHD. Moreover, in keeping with the increase of CCR6+ and CD161+ T cells, RORγt the key transcription factor that orchestrates the differentiation of Th17 cells, was significantly increased in the intestinal mucosa of patients with aGVHD compared with intestinal mucosa of patients without aGVHD (P=0.01). Since plasmacytoid dendritic cells (PDCs) have been reported to drive the differentiation of the Th17 subset, we quantified PDCs in these patients. PDC CD123+ cells were increased in the intestinal mucosa of patients with aGVHD. Furthermore, the number of CD123+ PDCs paralleled the histological grade of aGVHD, providing evidence for a role of Th17-mediated responses and a potential new pathophysiological link between PDCs and Th17 in human aGVHD.
authors.affiliation: EA4273 Biometadys, Faculté de Médecine, Université de Nantes, Nantes, France.
authors.forename: C
authors.initials: C
authors.lastname: Bossard
authors.forename: F
authors.initials: F
authors.lastname: Malard
authors.forename: J
authors.initials: J
authors.lastname: Arbez
authors.forename: P
authors.initials: P
authors.lastname: Chevallier
authors.forename: T
authors.initials: T
authors.lastname: Guillaume
authors.forename: J
authors.initials: J
authors.lastname: Delaunay
authors.forename: J-F
authors.initials: JF
authors.lastname: Mosnier
authors.forename: P
authors.initials: P
authors.lastname: Tiberghien
authors.forename: P
authors.initials: P
authors.lastname: Saas
authors.forename: M
authors.initials: M
authors.lastname: Mohty
authors.forename: B
authors.initials: B
authors.lastname: Gaugler
mesh_terms: D056704:Adaptive Immunity; D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006086:Graft vs Host Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019337:Hematologic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D054399:Receptors, CCR6 / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: C106311:CCR6 protein, human; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D054399:Receptors, CCR6