CCR6/CCR10-mediated plasmacytoid dendritic cell recruitment to inflamed epithelia after instruction in lymphoid tissues

• Published in: Blood Vol. 118; no. 19; pp. 5130 - 5140
• Main Authors: Sisirak, Vanja, Vey, Nelly, Vanbervliet, Béatrice, Duhen, Thomas, Puisieux, Isabelle, Homey, Bernhard, Bowman, Edward P., Trinchieri, Giorgio, Dubois, Bertrand, Kaiserlian, Dominique, Lira, Sergio A., Puisieux, Alain, Blay, Jean-Yves, Caux, Christophe, Bendriss-Vermare, Nathalie
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 10.11.2011; Americain Society of Hematology; American Society of Hematology
• Subjects: Adoptive Transfer; Animals; Biological and medical sciences; Cell Differentiation - immunology; Cell Movement - immunology; Chemokine CCL19 - pharmacology; Chemokine CCL20 - pharmacology; Dendritic Cells - immunology; Dendritic Cells - pathology; Epithelium - immunology; Epithelium - pathology; Female; Hematologic and hematopoietic diseases; Humans; Immunobiology; Inflammation - immunology; Inflammation - pathology; Interferon-alpha - biosynthesis; Interleukin-3 - pharmacology; Ligands; Lymphoid Tissue - immunology; Lymphoid Tissue - pathology; Medical sciences; Melanoma, Experimental - immunology; Melanoma, Experimental - pathology; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Immunological; Palatine Tonsil - cytology; Palatine Tonsil - immunology; Receptors, CCR10 - metabolism; Receptors, CCR6 - deficiency; Receptors, CCR6 - genetics; Receptors, CCR6 - metabolism; Toll-Like Receptor 7 - metabolism; Dendritic cell; Hematology; CCR10 chemokine receptor; Inflammation; Chemokine receptor; CC chemokine; Lymphoid tissue; Epithelium; Instruction; Plasmacytoid dendritic cell; Recruitment; Antigen presenting cell; CCR6 chemokine receptor
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2010-07-295626

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.