title: CCR6/CCR10-mediated plasmacytoid dendritic cell recruitment to inflamed epithelia after instruction in lymphoid tissues.
abstract: Absent in peripheral tissues during homeostasis, human plasmacytoid dendritic cells (pDCs) are described in inflamed skin or mucosa. Here, we report that, unlike blood pDCs, a subset of tonsil pDCs express functional CCR6 and CCR10, and their respective ligands CCL20 and CCL27are detected in inflamed epithelia contacting blood dendritic cell antigen 2(+) pDCs. Moreover, pDCs are recruited to imiquimod-treated skin tumors in WT but not CCR6-deficient mice, and competitive adoptive transfers reveal that CCR6-deficient pDCs are impaired in homing to inflamed skin tumors after intravenous transfer. On IL-3 culture, CCR6 and CCR10 expression is induced on human blood pDCs that become responsive to CCL20 and CCL27/CCL28, respectively. Interestingly, unlike myeloid DC, blood pDCs initially up-regulate CCR7 expression and CCL19 responsiveness on IL-3 ± CpG-B and then acquire functional CCR6 and CCR10. Finally, IL-3-differentiated CCR6(+) CCR10(+) pDCs secrete high levels of IFN-α in response to virus. Overall, we propose an unexpected pDCs migratory model that may best apply for mucosal-associated lymphoid tissues. After CCR7-mediated extravasation into lymphoid tissues draining inflamed epithelia, blood pDCs may be instructed to up-regulate CCR6 and/or CCR10 allowing their homing into inflamed epithelia (in mucosae or skin). At this site, pDCs can then produce IFN-α contributing to pathogen clearance and/or local inflammation.
authors.affiliation: Université de Lyon, France.
authors.forename: Vanja
authors.initials: V
authors.lastname: Sisirak
authors.forename: Nelly
authors.initials: N
authors.lastname: Vey
authors.forename: Béatrice
authors.initials: B
authors.lastname: Vanbervliet
authors.forename: Thomas
authors.initials: T
authors.lastname: Duhen
authors.forename: Isabelle
authors.initials: I
authors.lastname: Puisieux
authors.forename: Bernhard
authors.initials: B
authors.lastname: Homey
authors.forename: Edward P
authors.initials: EP
authors.lastname: Bowman
authors.forename: Giorgio
authors.initials: G
authors.lastname: Trinchieri
authors.forename: Bertrand
authors.initials: B
authors.lastname: Dubois
authors.forename: Dominique
authors.initials: D
authors.lastname: Kaiserlian
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Lira
authors.forename: Alain
authors.initials: A
authors.lastname: Puisieux
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
authors.forename: Christophe
authors.initials: C
authors.lastname: Caux
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bendriss-Vermare
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D054415:Chemokine CCL19 / Q000494:pharmacology; D054418:Chemokine CCL20 / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004848:Epithelium / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D016898:Interferon-alpha / Q000096:biosynthesis; D007377:Interleukin-3 / Q000494:pharmacology; D008024:Ligands; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018448:Models, Immunological; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D054447:Receptors, CCR10 / Q000378:metabolism*; D054399:Receptors, CCR6 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051199:Toll-Like Receptor 7 / Q000378:metabolism
chemical_list: C515706:CCR10 protein, human; C106311:CCR6 protein, human; C498126:CCR6 protein, mouse; C515707:Ccr10 protein, mouse; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D016898:Interferon-alpha; D007377:Interleukin-3; D008024:Ligands; D008562:Membrane Glycoproteins; D054447:Receptors, CCR10; D054399:Receptors, CCR6; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7