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Langerhans cells arise from monocytes in vivo

Abstract

Langerhans cells (LCs) are the only dendritic cells of the epidermis and constitute the first immunological barrier against pathogens and environmental insults. The factors regulating LC homeostasis remain elusive and the direct circulating LC precursor has not yet been identified in vivo. Here we report an absence of LCs in mice deficient in the receptor for colony-stimulating factor 1 (CSF-1) in steady-state conditions. Using bone marrow chimeric mice, we have established that CSF-1 receptor–deficient hematopoietic precursors failed to reconstitute the LC pool in inflamed skin. Furthermore, monocytes with high expression of the monocyte marker Gr-1 (also called Ly-6c/G) were specifically recruited to the inflamed skin, proliferated locally and differentiated into LCs. These results identify Gr-1hi monocytes as the direct precursors for LCs in vivo and establish the importance of the CSF-1 receptor in this process.

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Figure 1: LC development in CSF-1- and CSF-1R-deficient mice.
Figure 2: Function of CSF-1R in LC differentiation in vivo.
Figure 3: Gr-1hi monocytes infiltrate and proliferate in situ in ultraviolet irradiation–inflamed skin.
Figure 4: Bead-positive Gr-1hi monocytes differentiate into dermal macrophages and epidermal LCs in inflamed skin.
Figure 5: Skin-infiltrating Gr-1hi monocytes differentiate into LCs.
Figure 6: Adoptive transfer of Gr-1hi monocytes in vivo.

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Acknowledgements

Supported by the Association Francaise Contre le Cancer (F.G.), the German Research Foundation (F.T.), the National Institutes of Health (AI49653 to G.J.R., and CA32551 and CA26504 to E.R.S.), the American Society of Hematology (X.-M.D.) and the Leukemia and Lymphoma Society (X.-M.D.).

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Correspondence to Miriam Merad.

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Ginhoux, F., Tacke, F., Angeli, V. et al. Langerhans cells arise from monocytes in vivo. Nat Immunol 7, 265–273 (2006). https://doi.org/10.1038/ni1307

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