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

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

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.

Publication types

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

MeSH terms

  • Animals
  • Brain / immunology
  • Brain / metabolism
  • Cell Differentiation / genetics
  • Epidermis / immunology
  • Epidermis / metabolism
  • Homeostasis
  • Humans
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / metabolism
  • Interleukins / genetics
  • Interleukins / immunology
  • Interleukins / metabolism
  • Interleukins / physiology*
  • Keratinocytes / immunology
  • Keratinocytes / metabolism
  • Langerhans Cells / cytology
  • Langerhans Cells / immunology*
  • Langerhans Cells / metabolism
  • Mice
  • Microglia / cytology
  • Microglia / immunology*
  • Microglia / metabolism
  • Psoriasis / chemically induced
  • Psoriasis / immunology
  • Receptor, Macrophage Colony-Stimulating Factor / metabolism
  • Signal Transduction
  • Skin / immunology
  • Skin / metabolism
  • Stromal Cells / metabolism*

Substances

  • Interleukins
  • interleukin-34, human
  • interleukin-34, mouse
  • Receptor, Macrophage Colony-Stimulating Factor