Cutaneous CXCL14 targets blood precursors to epidermal niches for Langerhans cell differentiation.
Dendritic cells (DCs) are major constituents of peripheral tissues, where they control immunity to foreign and self-antigens. The process of continuous DC renewal under homeostatic conditions is largely undefined. Here, we demonstrate that CD14+ DC precursors, either derived from CD34+ hematopoietic progenitor cells or isolated from blood, were attracted by the chemokine CXCL14, which is constitutively produced in healthy skin and other epithelial tissues. In a tissue model we show that human epidermal equivalents profoundly affected CD14+ DC precursors, including their suprabasal positioning and survival as well as their differentiation into Langerhans cell-like cells with potent antigen-presentation functions. Our model assigns unprecedented roles to CXCL14 and epidermal tissue as attractant and niche of differentiation, respectively, in the renewal of Langerhans cells under steady-state conditions.
Schaerli
Patrick
P
Institute of Cell Biology, University of Bern, CH-3012 Bern, Switzerland.
Willimann
Katharina
K
Ebert
Lisa M
LM
Walz
Alfred
A
Moser
Bernhard
B
D002454:Cell Differentiation / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D019743:Chemokines, CXC / Q000276:immunology* / Q000378:metabolism; D018920:Coculture Techniques; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology*; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007801:Langerhans Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D018613:Microscopy, Confocal; D018448:Models, Immunological
C118056:CXCL14 protein, human; D019743:Chemokines, CXC