Pivotal Advance: Avian colony-stimulating factor 1 (CSF-1), interleukin-34 (IL-34), and CSF-1 receptor genes and gene products

Garceau, Valérie; Smith, Jacqueline; Paton, Ian R.; Davey, Megan; Fares, Mario A.; Sester, David P.; Burt, David W.; Hume, David

doi:10.1189/jlb.0909624

Cited by 154 publications

(184 citation statements)

References 71 publications

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“…These findings suggest that the IL-34 gene is a unique target of 1α,25(OH) 2 (28)(29)(30)(31). At the amino acid sequence level, IL-34 gene is more conserved than the CSF-1 gene during evolution (32). These results suggest that the vitamin D system and IL-34 may fundamentally work in normal angiogenesis.…”

Section: Discussionmentioning

confidence: 56%

Spleen serves as a reservoir of osteoclast precursors through vitamin D-induced IL-34 expression in osteopetrotic op/op mice

Nakamichi¹,

Mizoguchi²,

Arai³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Osteoclasts are generated from monocyte/macrophage-lineage precursors in response to colony-stimulating factor 1 (CSF-1) and receptor activator of nuclear factor-κB ligand (RANKL). CSF-1-mutated CSF-1 op/op mice as well as RANKL −/− mice exhibit osteopetrosis (OP) caused by osteoclast deficiency. We previously identified RANKL receptor (RANK)/CSF-1 receptor (CSF-1R) double-positive cells as osteoclast precursors (OCPs), which existed in bone in RANKL −/− mice. Here we show that OCPs do not exist in bone but in spleen in CSF-1 op/op mice, and spleen acts as their reservoir. IL-34, a newly discovered CSF-1R ligand, was highly expressed in vascular endothelial cells in spleen in CSF-1 op/op mice. Vascular endothelial cells in bone also expressed IL-34, but its expression level was much lower than in spleen, suggesting a role of IL-34 in the splenic generation of OCPs. Splenectomy (SPX) blocked CSF-1-induced osteoclastogenesis in CSF-1 op/op mice. Osteoclasts appeared in aged CSF-1 op/op mice with up-regulation of IL-34 expression in spleen and bone. Splenectomy blocked the age-associated appearance of osteoclasts. The injection of 2-methylene-19-nor-(20S)-1α,25(OH) 2 D 3 (2MD), a potent analog of 1α,25-dihidroxyvitamin D 3 , into CSF-1 op/op mice induced both hypercalcemia and osteoclastogenesis. Administration of 2MD enhanced IL-34 expression not only in spleen but also in bone through a vitamin D receptor-mediated mechanism. Either splenectomy or siRNA-mediated knockdown of IL-34 suppressed 2MD-induced osteoclastogenesis. These results suggest that IL-34 plays a pivotal role in maintaining the splenic reservoir of OCPs, which are transferred to bone in response to diverse stimuli, in CSF-1 op/op mice. The present study also suggests that the IL-34 gene in vascular endothelial cells is a unique target of vitamin D. CSF-1 is the most potent growth factor for monocytes/macrophages (3), but its synthesis by osteoblasts occurs independently of PTH and 1α,25(OH) 2 D 3 (2). CSF-1 op/op mice cannot produce a functionally active CSF-1 (4), and therefore, exhibit monocytopenia and osteopetrosis (OP) (5, 6). However, several curious phenomena have been observed in CSF-1 op/op mice. First, osteoclasts are totally absent in young CSF-1 op/op mice, but appear in aged CSF-1 op/op mice (7). Second, osteopetrotic characteristics of CSF-1R −/− mice are more severe than those of CSF-1 op/op mice (8). Third, F4/80 + [F4/80(+)] macrophages exist in the splenic red pulp in CSF-1 op/op mice as well as in WT mice, and their number is regulated by a mechanism independently of CSF-1 (9, 10). Fourth, the administration of vascular endothelial growth factor (VEGF) rescues osteopetrosis in CSF-1 op/op mice (11, 12), but VEGF cannot substitute for CSF-1 to induce osteoclast formation in vitro (13).Recently, Lin et al. (14) discovered IL-34, as a new ligand for CSF-1R. The amino acid sequence of IL-34 was quite different from that of CSF-1, but IL-34 promoted macrophage colony formation like CSF-1 did. IL-34 was specifically expressed in splen...

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Section: Discussionmentioning

confidence: 56%

Spleen serves as a reservoir of osteoclast precursors through vitamin D-induced IL-34 expression in osteopetrotic op/op mice

Nakamichi¹,

Mizoguchi²,

Arai³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…We next tested the involvement of CD115, until now the only receptor for IL-34 described outside the CNS (24,25), which is only expressed by monocytes and macrophages, conventional DCs (cDCs), and pDCs, and not by CD4 + T cells (26,27). We used an anti-CD115-blocking Ab that has been previously shown to inhibit M-CSF action in both rats and mice (28).…”

Section: Cd25mentioning

confidence: 99%

“…In addition, we have demonstrated the involvement of IFN-γ and FGL2 in this process; however, some suppression remains after blockade of the IFN-γ and FGL2 inhibitory effect (18,21,22). To address whether IL-34 is involved in CD8 + CD40Ig Treg suppression, we tested a neutralizing anti-IL-34 Ab in the suppressive mixed lymphocyte reaction (MLR) assay ( Figure 1C and Supplemental Figure 2A) lo Tregs (Supplemental Figure 3A), and that IL-34 and M-CSF use the same receptor in the macrophage lineage cells and DCs (24,25), we investigated the possibility that M-CSF could play a role in the suppression of effector CD4 +…”

Section: Introductionmentioning

confidence: 99%

IL-34 is a Treg-specific cytokine and mediates transplant tolerance

Bézie¹,

Picarda²,

Ossart³

et al. 2015

Journal of Clinical Investigation

107

142

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“…These cells comprise 10-15% of the total cells in most organs of the body, and are especially concentrated adjacent to mucosal surfaces (5). Their differentiation and maturation are controlled by hemopoietic growth factors, notably CSF-1 and IL-34, which share a receptor encoded by the c-fms protooncogene (6,7).…”

mentioning

confidence: 99%

Pig Bone Marrow-Derived Macrophages Resemble Human Macrophages in Their Response to Bacterial Lipopolysaccharide

Kapétanovic

Fairbairn

Beraldi

et al. 2012

The Journal of Immunology

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119

137

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Mouse bone marrow-derived macrophages (BMDM) grown in M-CSF (CSF-1) have been used widely in studies of macrophage biology and the response to TLR agonists. We investigated whether similar cells could be derived from the domestic pig using human rCSF-1 and whether porcine macrophages might represent a better model of human macrophage biology. Cultivation of pig bone marrow cells for 5–7 d in presence of human rCSF-1 generated a pure population of BMDM that expressed the usual macrophage markers (CD14, CD16, and CD172a), were potent phagocytic cells, and produced TNF in response to LPS. Pig BMDM could be generated from bone marrow cells that had been stored frozen and thawed so that multiple experiments can be performed on samples from a single animal. Gene expression in pig BMDM from outbred animals responding to LPS was profiled using Affymetrix microarrays. The temporal cascade of inducible and repressible genes more closely resembled the known responses of human than mouse macrophages, sharing with humans the regulation of genes involved in tryptophan metabolism (IDO, KYN), lymphoattractant chemokines (CCL20, CXCL9, CXCL11, CXCL13), and the vitamin D3-converting enzyme, Cyp27B1. Conversely, in common with published studies of human macrophages, pig BMDM did not strongly induce genes involved in arginine metabolism, nor did they produce NO. These results establish pig BMDM as an alternative tractable model for the study of macrophage transcriptional control.

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Pivotal Advance: Avian colony-stimulating factor 1 (CSF-1), interleukin-34 (IL-34), and CSF-1 receptor genes and gene products

Cited by 154 publications

References 71 publications

Spleen serves as a reservoir of osteoclast precursors through vitamin D-induced IL-34 expression in osteopetrotic op/op mice

Spleen serves as a reservoir of osteoclast precursors through vitamin D-induced IL-34 expression in osteopetrotic op/op mice

IL-34 is a Treg-specific cytokine and mediates transplant tolerance

Pig Bone Marrow-Derived Macrophages Resemble Human Macrophages in Their Response to Bacterial Lipopolysaccharide

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