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

By Yaming Wang, Kristy J. Szretter, W. Vermi, S. Gilfillan, Cristina Rossini, M. Cella, A. Barrow, Michael S. Diamond, M. Colonna. Nature Immunology, 2012

926 citations recorded by the source corpus.

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 (Il34LacZ/LacZ) reporter mice, we found that keratinocytes and neurons were the main sources of IL-34. Il34LacZ/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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/0b89351d37e9ab1cf5fa8071b98c8540f7057fbe

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In Immunology

1. C. Iadecola
2. M. Guilliams
3. H. Hammad
4. B. Lambrecht
5. Miriam Merad
6. J. Anrather
7. C. Secombes
8. J. Zou

Citations in the corpus

• Origin and Functions of Tissue Macrophages (2014, background): “After birth, a massive expansion of microglia cell numbers is driven exclusively through in situ proliferation via M-CSF and interleukin-34 (IL-34) without monocyte input (Wegiel et al., 1998; Wang et al., 2012; Ginhoux et al., 2010; Ajami et al., 2007).”
• INTERLEUKIN-4- AND INTERLEUKIN-13-MEDIATED ALTERNATIVELY ACTIVATED MACROPHAGES: ROLES IN HOMEOSTASIS AND DISEASE (2013, positive): “In addition, although most bone marrow–derived populations depend primarily on colonystimulating factor 1 (CSF-1) signaling via CSF1-R for their development and survival, some self-renewing tissue macrophages, in particular microglia, require tissue-restricted signals derived exclusively from the al”
• Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases. (2016, background): “The receptor for IL-34 is colony-stimulating factor 1 receptor, and it is required for the development of Langerhans cells and microglia.(191) IL-34 stimulatesmonocyte andmacrophage proliferation and development.”
• Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023, background): “IL-34, a tissue-restricted ligand of CSF1R, is also required for the development of microglia.(68) Mature microglia also require CSF1R signaling, as demonstrated by the significant loss of microglia in adult mice treated with Csf-1R inhibitors.”