Abstract

The differentiation of bone marrow-derived progenitor cells into monocytes, tissue macrophages and some dendritic cell (DC) subtypes requires the growth factor CSF1 and its receptor, CSF1R. Langerhans cells (LCs) and microglia develop from embryonic myeloid precursor cells that populate the epidermis and central nervous system (CNS) before birth. Notably, LCs and microglia are present in CSF1-deficient mice but absent from CSF1R-deficient mice. Here we investigated whether an alternative CSF1R ligand, interleukin 34 (IL-34), is responsible for this discrepancy. Through the use of IL-34-deficient (Il34(LacZ/LacZ)) reporter mice, we found that keratinocytes and neurons were the main sources of IL-34. Il34(LacZ/LacZ) mice selectively lacked LCs and microglia and responded poorly to skin antigens and viral infection of the CNS. Thus, IL-34 specifically directs the differentiation of myeloid cells in the skin epidermis and CNS.

Links

Publisher Full Text

Authors

Wang Y, Szretter KJ, Vermi W, Gilfillan S, Rossini C, Cella M, Barrow AD, Diamond MS, Colonna M

Institution

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

Source

Nature immunology 13:8 2012 pg 753-60

MeSH

Animals
Cell Differentiation
Central Nervous System
Interleukins
Keratinocytes
Langerhans Cells
Macrophage Colony-Stimulating Factor
Macrophages
Mice
Mice, Inbred C57BL
Mice, Knockout
Microglia
Myeloid Cells
Myelopoiesis
Neurons
Receptor, Macrophage Colony-Stimulating Factor
Skin
West Nile Fever
West Nile virus

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22729249