TY - JOUR
T1 - Stroma-Derived Interleukin-34 Controls the Development and Maintenance of Langerhans Cells and the Maintenance of Microglia
AU - Greter, Melanie
AU - Lelios, Iva
AU - Pelczar, Pawel
AU - Hoeffel, Guillaume
AU - Price, Jeremy
AU - Leboeuf, Marylene
AU - Kündig, Thomas M.
AU - Frei, Karl
AU - Ginhoux, Florent
AU - Merad, Miriam
AU - Becher, Burkhard
N1 - Funding Information:
B.B. is supported by the Swiss National Science Foundation and the European Union FP7 project TargetBraIn (279017). M.M. is supported by NIH grants CA112100, HL086899, and AI080884. M.G. is supported by the Forschungskredit of the University of Zurich. F.G. is supported by the Singapore Immunology Network core grant. We also acknowledge the Neuroscience Center Zurich, University of Zurich, and ETH Zurich, Switzerland. We thank Andrew L. Croxford for critical reading of the manuscript.
PY - 2012/12/14
Y1 - 2012/12/14
N2 - Colony stimulating factor-1 (Csf-1) receptor and its ligand Csf-1 control macrophage development, maintenance, and function. The development of both Langerhans cells (LCs) and microglia is highly dependent on Csf-1 receptor signaling but independent of Csf-1. Here we show that in both mice and humans, interleukin-34 (IL-34), an alternative ligand for Csf-1 receptor, is produced by keratinocytes in the epidermis and by neurons in the brain. Mice lacking IL-34 displayed a marked reduction of LCs and a decrease of microglia, whereas monocytes, dermal, and lymphoid tissue macrophages and DCs were unaffected. We identified IL-34 as a nonredundant cytokine for the development of LCs during embryogenesis as well as for their homeostasis in the adult skin. Whereas inflammation-induced repopulation of LCs appears to be dependent on Csf-1, once inflammation is resolved, LC survival is again IL-34-dependent. In contrast, microglia and their yolk sac precursors develop independently of IL-34 but rely on it for their maintenance in the adult brain.
AB - Colony stimulating factor-1 (Csf-1) receptor and its ligand Csf-1 control macrophage development, maintenance, and function. The development of both Langerhans cells (LCs) and microglia is highly dependent on Csf-1 receptor signaling but independent of Csf-1. Here we show that in both mice and humans, interleukin-34 (IL-34), an alternative ligand for Csf-1 receptor, is produced by keratinocytes in the epidermis and by neurons in the brain. Mice lacking IL-34 displayed a marked reduction of LCs and a decrease of microglia, whereas monocytes, dermal, and lymphoid tissue macrophages and DCs were unaffected. We identified IL-34 as a nonredundant cytokine for the development of LCs during embryogenesis as well as for their homeostasis in the adult skin. Whereas inflammation-induced repopulation of LCs appears to be dependent on Csf-1, once inflammation is resolved, LC survival is again IL-34-dependent. In contrast, microglia and their yolk sac precursors develop independently of IL-34 but rely on it for their maintenance in the adult brain.
UR - https://www.scopus.com/pages/publications/84870907320
U2 - 10.1016/j.immuni.2012.11.001
DO - 10.1016/j.immuni.2012.11.001
M3 - Article
C2 - 23177320
AN - SCOPUS:84870907320
SN - 1074-7613
VL - 37
SP - 1050
EP - 1060
JO - Immunity
JF - Immunity
IS - 6
ER -