Dermal-resident CD14+ cells differentiate into Langerhans cells

Abstract

Epidermal Langerhans cells (LCs) show extraordinary immunostimulatory capacity and play a key role in the initiation and regulation of immune responses. Studies of LC biology are currently the focus of efforts to engineer immune responses and to better understand the immunopathology of cutaneous diseases. Here we identified and characterized a population of LC precursors that were resident in human skin. These immediate precursors expressed CD14, langerin and functional CCR6. When cultured with transforming growth factor-β1 alone, they had the potential to differentiate into epidermal LCs; when cultured in the presence of granulocyte macrophage–colony-stimulating factor and interleukin 4 they differentiated into functionally mature dendritic cells. Identification and characterization of these LC precursors provided insight into LC biology and the mechanism(s) through which LCs repopulate the epidermis.

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Figure 1: Comparative phenotypes of different skin migratory cell populations and detection of S-100, CD68 and FXIIIa in miCD14+ and miCD14 cell cytoplasm.
Figure 2: Morphology of miCD14+ and miCD14 cells.
Figure 3: Differentiation of miCD14+ cells into LCs in the presence of various cytokine combinations.
Figure 4: CD14+ cells reside in dermis and migrate actively from skin explants.
Figure 5: miCD14+ and mCD14 cells show distinct capacities for antigen uptake.
Figure 6: miCD14 + cells express CCR6 and migrate in response to the CCR6 ligand MIP-3α.
Figure 7: GM-CSF, IL-4 and TGF-β1 do not induce proliferation of miCD14+ cells, whereas TGF-β1 alone or in combination with GM-CSF + IL-4 increases viability of miCD14+ cells.
Figure 8: Distinct allostimulatory capacity of miCD14+ cells that differentiated into LCs in response to various cytokines.

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Acknowledgements

We thank F. Shagas and A. C. Bursick for technical assistance and personnel from Magee Women's Hospital for human skin samples. Supported by the Dermatology Foundation (A. T. L.) and grants from the American Heart Association (to A. E. M.) and National Institutes of Health: RO1 AI43916 and PO1 CA73743 (to L. D. F.) and RO1 DK49745 and RO1 AI41011 (to A. W. T.).

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Correspondence to Adriana T. Larregina or Louis D. Falo Jr..

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Larregina, A., Morelli, A., Spencer, L. et al. Dermal-resident CD14+ cells differentiate into Langerhans cells. Nat Immunol 2, 1151–1158 (2001) doi:10.1038/ni731

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