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

  1. Author:
    Sisirak, V.
    Vey, N.
    Vanbervliet, B.
    Duhen, T.
    Puisieux, I.
    Homey, B.
    Bowman, E. P.
    Trinchieri, G.
    Dubois, B.
    Kaiserlian, D.
    Lira, S. A.
    Puisieux, A.
    Blay, J. Y.
    Caux, C.
    Bendriss-Vermare, N.

  2. Author Address

    [Sisirak, V; Vey, N; Vanbervliet, B; Puisieux, I; Puisieux, A; Blay, JY; Caux, C; Bendriss-Vermare, N] Univ Lyon 1, Inst Sci Pharmaceut & Biol, F-69365 Lyon, France. [Sisirak, V; Vey, N; Vanbervliet, B; Puisieux, I; Puisieux, A; Blay, JY; Caux, C; Bendriss-Vermare, N] Ctr Rech Cancerol Lyon, INSERM, U1052, Lyon, France. [Sisirak, V; Vey, N; Vanbervliet, B; Puisieux, I; Puisieux, A; Blay, JY; Caux, C; Bendriss-Vermare, N] Ctr Rech Cancerol Lyon, Ctr Natl Rech Sci, UMR 5286, Lyon, France. [Sisirak, V; Vey, N; Puisieux, I; Puisieux, A; Blay, JY; Caux, C; Bendriss-Vermare, N] LabEx DEVweCAN, Lyon, France. [Duhen, T] Benaroya Res Inst, Program Immunol, Seattle, WA USA. [Homey, B] Univ Dusseldorf, Dept Dermatol, D-4000 Dusseldorf, Germany. [Bowman, EP] Schering Plough Biopharma, Dept Immunol, Palo Alto, CA USA. [Trinchieri, G] NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21701 USA. [Dubois, B; Kaiserlian, D] Inst Federatif Rech, INSERM, Equipe Immunite Infect & Vaccinat, U851, Lyon, France. [Lira, SA] Mt Sinai Sch Med, Inst Immunol, New York, NY USA. [Puisieux, A] Inst Univ France, Paris, France.;Bendriss-Vermare, N (reprint author), Ctr Leon Berard, Ctr Rech Cancerol Lyon, INSERM, Ctr Natl Rech Sci 5286,UMR 1052, 28 Rue Laennec, F-69373 Lyon 08, France;nathalie.bendriss-vermare@lyon.unicancer.fr
    1. Year: 2011
    2. Date: Nov
  2. Journal: Blood
    1. 118
    2. 19
    3. Pages: 5130-5140
  4. Type of Article: Article
  5. ISSN: 0006-4971
  1. 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 CCL27 are 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 upregulate 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-alpha 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-alpha contributing to pathogen clearance and/ or local inflammation. (Blood. 2011;118(19):5130-5140)

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External Sources

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  2. DOI: 10.1182/blood-2010-07-295626
  3. View record in Web of Science®
  4. WOS: 000296867100014

Library Notes

  1. Fiscal Year: FY2011-2012
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