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

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

doi:10.1038/ni.2360

Cited by 792 publications

(870 citation statements)

References 59 publications

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“…Both in vitro and when expressed in vivo under the control of the CSF-1 promoter, the biological activities of homodimeric glycoprotein interleukin-34 (IL-34) resemble those of the secreted glycoprotein isoform of CSF-1 (Wei et al 2010). Although there are significant differences in their signaling through the CSF-1R (Chihara et al 2010), it is primarily the differential expression of IL-34 and CSF-1 (Wei et al 2010;Greter et al 2012;Nandi et al 2012;Wang et al 2012) that results in their differential spatiotemporal regulation through the CSF-1R in vivo (Wei et al 2010;Nandi et al 2012). The transmembrane and proteoglycan CSF-1 isoforms act locally (Wiktor-Jedrzejczak et al 1991;Sundquist et al 1995;Van Nguyen and Pollard 2002;Dai et al 2004;Nandi et al 2006).…”

Section: Csf-1r Expressionmentioning

confidence: 99%

CSF-1 Receptor Signaling in Myeloid Cells

Stanley

Chiţu

2014

Cold Spring Harbor Perspectives in Biology

563

491

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The CSF-1 receptor (CSF-1R) is activated by the homodimeric growth factors colony-stimulating factor-1 (CSF-1) and interleukin-34 (IL-34). It plays important roles in development and in innate immunity by regulating the development of most tissue macrophages and osteoclasts, of Langerhans cells of the skin, of Paneth cells of the small intestine, and of brain microglia. It also regulates the differentiation of neural progenitor cells and controls functions of oocytes and trophoblastic cells in the female reproductive tract. Owing to this broad tissue expression pattern, it plays a central role in neoplastic, inflammatory, and neurological diseases. In this review we summarize the evolution, structure, and regulation of expression of the CSF-1R gene. We discuss the structures of CSF-1, IL-34, and the CSF-1R and the mechanism of ligand binding to and activation of the receptor. We further describe the pathways regulating macrophage survival, proliferation, differentiation, and chemotaxis downstream from the CSF-1R.

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Section: Csf-1r Expressionmentioning

confidence: 99%

CSF-1 Receptor Signaling in Myeloid Cells

Stanley

Chiţu

2014

Cold Spring Harbor Perspectives in Biology

563

491

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“…The maintenance and survival of microglia also depends on signaling at colony stimulating factor 1 receptor (CSF1R). The cytokine IL-34, which is primarily produced by neurons in the CNS, was identified as a separate ligand for CSF1R with a unique spatial distribution in the CNS; mice deficient in IL-34 have reduced numbers of microglia compared with wild-type mice, but only localized to brain regions where IL-34 would normally be expressed, including the cerebral cortex, basal ganglia, and hippocampus (Greter et al, 2012;Lin et al, 2008;Wang et al, 2012b). Moreover, microglia are curiously found in higher densities in regions that either produce or receive dopamine (Lawson et al, 1990), suggesting some unknown chemotactic or proliferation signal.…”

Section: Future Research Directions and Clinical Implicationsmentioning

confidence: 99%

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

Lacagnina

Rivera

Bilbo

2016

Neuropsychopharmacol

210

164

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Drugs of abuse cause persistent alterations in synaptic plasticity that may underlie addiction behaviors. Evidence suggests glial cells have an essential and underappreciated role in the development and maintenance of drug abuse by influencing neuronal and synaptic functions in multifaceted ways. Microglia and astrocytes perform critical functions in synapse formation and refinement in the developing brain, and there is growing evidence that disruptions in glial function may be implicated in numerous neurological disorders throughout the lifespan. Linking evidence of function in health and under pathological conditions, this review will outline the glial and neuroimmune mechanisms that may contribute to drug-abuse liability, exploring evidence from opioids, alcohol, and psychostimulants. Drugs of abuse can activate microglia and astrocytes through signaling at innate immune receptors, which in turn influence neuronal function not only through secretion of soluble factors (eg, cytokines and chemokines) but also potentially through direct remodeling of the synapses. In sum, this review will argue that neural-glial interactions represent an important avenue for advancing our understanding of substance abuse disorders.

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“…3), which is expressed primarily on mononuclear phagocytic cells and their precursors (4). Interleukin-34 (IL34) is a second ligand for CSF-1R; it controls the development of specific macrophage lineages, such as microglia and Langerhans cells (5). IL34 and CSF-1 have distinct expression patterns (6).…”

Section: Introductionmentioning

confidence: 99%

The Promotion of Breast Cancer Metastasis Caused by Inhibition of CSF-1R/CSF-1 Signaling Is Blocked by Targeting the G-CSF Receptor

Swierczak

Cook

Lenzo

et al. 2014

Cancer Immunology Research

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Treatment options are limited for patients with breast cancer presenting with metastatic disease. Targeting of tumor-associated macrophages through the inhibition of colony-stimulating factor-1 receptor (CSF-1R), a key macrophage signaling pathway, has been reported to reduce tumor growth and metastasis, and these treatments are now in clinical trials. Here, we report that, surprisingly, treatment with neutralizing anti-CSF-1R and anti-CSF-1 antibodies, or with two different small-molecule inhibitors of CSF-1R, could actually increase spontaneous metastasis without altering primary tumor growth in mice bearing two independently derived mammary tumors. The blockade of CSF-1R or CSF-1 led to increased levels of serum G-CSF, increased frequency of neutrophils in the primary tumor and in the metastasis-associated lung, as well as increased numbers of neutrophils and Ly6C hi monocytes in the peripheral blood. Neutralizing antibody against the G-CSF receptor, which regulates neutrophil development and function, reduced the enhanced metastasis and neutrophil numbers that resulted from CSF-1R blockade. These results indicate that the role of the CSF-1R/CSF-1 system in breast cancer is far more complex than originally proposed, and requires further investigation as a therapeutic target. Cancer Immunol Res; 2(8); 765-76. Ó2014 AACR.

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

Cited by 792 publications

References 59 publications

CSF-1 Receptor Signaling in Myeloid Cells

CSF-1 Receptor Signaling in Myeloid Cells

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

The Promotion of Breast Cancer Metastasis Caused by Inhibition of CSF-1R/CSF-1 Signaling Is Blocked by Targeting the G-CSF Receptor

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