IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia

Yaming Wang, Kristy J. Szretter, William Vermi, Susan Gilfillan, Cristina Rossini, Marina Cella, Alexander D. Barrow, Michael S. Diamond, Marco Colonna

Research output: Contribution to journalArticlepeer-review

579 Scopus citations

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.

Original languageEnglish
Pages (from-to)753-760
Number of pages8
JournalNature immunology
Volume13
Issue number8
DOIs
StatePublished - Aug 2012

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