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Immunity. 2012 Dec 14;37(6):1050-1060. doi: 10.1016/j.immuni.2012.11.001. Epub 2012 Nov 21.

Stroma-derived interleukin-34 controls the development and maintenance of langerhans cells and the maintenance of microglia.

Author information

1
Institute of Experimental Immunology, Neuroimmunology, University of Zürich, CH 8006 Zürich, Switzerland.
2
Institute of Laboratory Animal Science, University of Zürich, CH 8006 Zürich, Switzerland.
3
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), BIOPOLIS, 138648, Singapore.
4
Department of Oncological Sciences, New York, NY 10029, USA.
5
The Immunology Institute, New York, NY 10029, USA.
6
Clinical Tumor Biology & Immunotherapy Unit, University Hospital Zürich, 8091 Zürich, Switzerland.
7
Department of Neurosurgery, University Hospital Zürich, 8091 Zürich, Switzerland.
8
Tisch Cancer Institute Mount Sinai School of Medicine, New York, NY 10029, USA.
#
Contributed equally

Abstract

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.

PMID:
23177320
PMCID:
PMC4291117
DOI:
10.1016/j.immuni.2012.11.001
[Indexed for MEDLINE]
Free PMC Article

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