IL-34 induces the differentiation of human monocytes into immunosuppressive macrophages. antagonistic effects of GM-CSF and IFNγ.
IL-34 is a recently identified cytokine that signals via the M-CSF receptor and promotes monocyte survival. Depending on the environment, monocytes can differentiate into macrophages (Mφ) or dendritic cells (DC). A wide spectrum of Mφ and DC subsets, with distinct phenotypes and functions, has been...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3568045?pdf=render |
| _version_ | 1819213324279087104 |
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| author | Etienne D Foucher Simon Blanchard Laurence Preisser Erwan Garo Norbert Ifrah Philippe Guardiola Yves Delneste Pascale Jeannin |
| author_facet | Etienne D Foucher Simon Blanchard Laurence Preisser Erwan Garo Norbert Ifrah Philippe Guardiola Yves Delneste Pascale Jeannin |
| author_sort | Etienne D Foucher |
| collection | DOAJ |
| description | IL-34 is a recently identified cytokine that signals via the M-CSF receptor and promotes monocyte survival. Depending on the environment, monocytes can differentiate into macrophages (Mφ) or dendritic cells (DC). A wide spectrum of Mφ and DC subsets, with distinct phenotypes and functions, has been described. To date, the phenotype of monocytes exposed to IL-34 remains unexplored. We report here that IL-34 induces the differentiation of monocytes into CD14(high) CD163(high) CD1a(-) Mφ (IL-34-Mφ). Upon LPS stimulation, IL-34-Mφ exhibit an IL-10(high) IL-12(low) M2 profile and express low levels of the costimulatory molecules CD80 and CD86. IL-34-Mφ exhibit poor T cell costimulatory properties, and have potent immunosuppressive properties (decrease of TCR-stimulated T cell proliferation). For all the parameters analyzed, IL-34-Mφ are phenotypically and functionally similar to M-CSF-Mφ. IL-34 appears as efficient as M-CSF in inducing the generation of immunosuppressive Mφ. Moreover, the generation of IL-34-Mφ is mediated through the M-CSF receptor, is independent of endogenous M-CSF consumption and is potentiated by IL-6. In an attempt to identify strategies to prevent a deleterious M2 cell accumulation in some pathological situations, we observed that IFNγ and GM-CSF prevent the generation of immunosuppressive Mφ induced by IL-34. IFNγ also switches established IL-34-Mφ into immunostimulatory Mφ. In conclusion, we demonstrate that IL-34 drives the differentiation of monocytes into immunosuppressive M2, in a manner similar to M-CSF, and that IFNγ and GM-CSF prevent this effect. |
| first_indexed | 2024-12-23T06:57:03Z |
| format | Article |
| id | doaj.art-ef78c7b403b14d2f89636f0b012e8045 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T06:57:03Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ef78c7b403b14d2f89636f0b012e80452022-12-21T17:56:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5604510.1371/journal.pone.0056045IL-34 induces the differentiation of human monocytes into immunosuppressive macrophages. antagonistic effects of GM-CSF and IFNγ.Etienne D FoucherSimon BlanchardLaurence PreisserErwan GaroNorbert IfrahPhilippe GuardiolaYves DelnestePascale JeanninIL-34 is a recently identified cytokine that signals via the M-CSF receptor and promotes monocyte survival. Depending on the environment, monocytes can differentiate into macrophages (Mφ) or dendritic cells (DC). A wide spectrum of Mφ and DC subsets, with distinct phenotypes and functions, has been described. To date, the phenotype of monocytes exposed to IL-34 remains unexplored. We report here that IL-34 induces the differentiation of monocytes into CD14(high) CD163(high) CD1a(-) Mφ (IL-34-Mφ). Upon LPS stimulation, IL-34-Mφ exhibit an IL-10(high) IL-12(low) M2 profile and express low levels of the costimulatory molecules CD80 and CD86. IL-34-Mφ exhibit poor T cell costimulatory properties, and have potent immunosuppressive properties (decrease of TCR-stimulated T cell proliferation). For all the parameters analyzed, IL-34-Mφ are phenotypically and functionally similar to M-CSF-Mφ. IL-34 appears as efficient as M-CSF in inducing the generation of immunosuppressive Mφ. Moreover, the generation of IL-34-Mφ is mediated through the M-CSF receptor, is independent of endogenous M-CSF consumption and is potentiated by IL-6. In an attempt to identify strategies to prevent a deleterious M2 cell accumulation in some pathological situations, we observed that IFNγ and GM-CSF prevent the generation of immunosuppressive Mφ induced by IL-34. IFNγ also switches established IL-34-Mφ into immunostimulatory Mφ. In conclusion, we demonstrate that IL-34 drives the differentiation of monocytes into immunosuppressive M2, in a manner similar to M-CSF, and that IFNγ and GM-CSF prevent this effect.http://europepmc.org/articles/PMC3568045?pdf=render |
| spellingShingle | Etienne D Foucher Simon Blanchard Laurence Preisser Erwan Garo Norbert Ifrah Philippe Guardiola Yves Delneste Pascale Jeannin IL-34 induces the differentiation of human monocytes into immunosuppressive macrophages. antagonistic effects of GM-CSF and IFNγ. PLoS ONE |
| title | IL-34 induces the differentiation of human monocytes into immunosuppressive macrophages. antagonistic effects of GM-CSF and IFNγ. |
| title_full | IL-34 induces the differentiation of human monocytes into immunosuppressive macrophages. antagonistic effects of GM-CSF and IFNγ. |
| title_fullStr | IL-34 induces the differentiation of human monocytes into immunosuppressive macrophages. antagonistic effects of GM-CSF and IFNγ. |
| title_full_unstemmed | IL-34 induces the differentiation of human monocytes into immunosuppressive macrophages. antagonistic effects of GM-CSF and IFNγ. |
| title_short | IL-34 induces the differentiation of human monocytes into immunosuppressive macrophages. antagonistic effects of GM-CSF and IFNγ. |
| title_sort | il 34 induces the differentiation of human monocytes into immunosuppressive macrophages antagonistic effects of gm csf and ifnγ |
| url | http://europepmc.org/articles/PMC3568045?pdf=render |
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