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- Publisher Website: 10.1002/eji.201646482
- Scopus: eid_2-s2.0-84989285256
- PMID: 27601030
- WOS: WOS:000392940400013
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Article: iRhom2 regulates CSF1R cell surface expression and non-steady state myelopoiesis in mice
Title | iRhom2 regulates CSF1R cell surface expression and non-steady state myelopoiesis in mice |
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Authors | |
Keywords | iRhom2 metalloprotease CSF1R myelopoiesis ADAM17 |
Issue Date | 2016 |
Citation | European Journal of Immunology, 2016, v. 46, n. 12, p. 2737-2748 How to Cite? |
Abstract | © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. CSF1R (colony stimulating factor 1 receptor) is the main receptor for CSF1 and has crucial roles in regulating myelopoeisis. CSF1R can be proteolytically released from the cell surface by ADAM17 (A disintegrin and metalloprotease 17). Here, we identified CSF1R as a major substrate of ADAM17 in an unbiased degradomics screen. We explored the impact of CSF1R shedding by ADAM17 and its upstream regulator, inactive rhomboid protein 2 (iRhom2, gene name Rhbdf2), on homeostatic development of mouse myeloid cells. In iRhom2-/- mice, we found constitutive accumulation of membrane-bound CSF1R on myeloid cells at steady state, although cell numbers of these populations were not altered. However, in the context of mixed bone marrow (BM) chimera, under competitive pressure, iRhom2-/- BM progenitor-derived monocytes, tissue macrophages and lung DCs showed a repopulation advantage over those derived from wild-type (WT) BM progenitors, suggesting enhanced CSF1R signaling in the absence of iRhom2. In vitro experiments indicate that iRhom2-/- Lin−SCA-1+c-Kit+ (LSKs) cells, but not granulocyte-macrophage progenitors (GMPs), had faster growth rates than WT cells in response to CSF1. Our results shed light on an important role of iRhom2/ADAM17 pathway in regulation of CSF1R shedding and repopulation of monocytes, macrophages and DCs. |
Persistent Identifier | http://hdl.handle.net/10722/292974 |
ISSN | 2021 Impact Factor: 6.688 2020 SCImago Journal Rankings: 2.272 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Qing, Xiaoping | - |
dc.contributor.author | D. Rogers, Lindsay | - |
dc.contributor.author | Mortha, Arthur | - |
dc.contributor.author | Lavin, Yonit | - |
dc.contributor.author | Redecha, Patricia | - |
dc.contributor.author | Issuree, Priya D. | - |
dc.contributor.author | Maretzky, Thorsten | - |
dc.contributor.author | Merad, Miriam | - |
dc.contributor.author | R. McIlwain, David | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Overall, Christopher M. | - |
dc.contributor.author | Blobel, Carl P. | - |
dc.contributor.author | Salmon, Jane E. | - |
dc.date.accessioned | 2020-11-17T14:57:36Z | - |
dc.date.available | 2020-11-17T14:57:36Z | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | European Journal of Immunology, 2016, v. 46, n. 12, p. 2737-2748 | - |
dc.identifier.issn | 0014-2980 | - |
dc.identifier.uri | http://hdl.handle.net/10722/292974 | - |
dc.description.abstract | © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. CSF1R (colony stimulating factor 1 receptor) is the main receptor for CSF1 and has crucial roles in regulating myelopoeisis. CSF1R can be proteolytically released from the cell surface by ADAM17 (A disintegrin and metalloprotease 17). Here, we identified CSF1R as a major substrate of ADAM17 in an unbiased degradomics screen. We explored the impact of CSF1R shedding by ADAM17 and its upstream regulator, inactive rhomboid protein 2 (iRhom2, gene name Rhbdf2), on homeostatic development of mouse myeloid cells. In iRhom2-/- mice, we found constitutive accumulation of membrane-bound CSF1R on myeloid cells at steady state, although cell numbers of these populations were not altered. However, in the context of mixed bone marrow (BM) chimera, under competitive pressure, iRhom2-/- BM progenitor-derived monocytes, tissue macrophages and lung DCs showed a repopulation advantage over those derived from wild-type (WT) BM progenitors, suggesting enhanced CSF1R signaling in the absence of iRhom2. In vitro experiments indicate that iRhom2-/- Lin−SCA-1+c-Kit+ (LSKs) cells, but not granulocyte-macrophage progenitors (GMPs), had faster growth rates than WT cells in response to CSF1. Our results shed light on an important role of iRhom2/ADAM17 pathway in regulation of CSF1R shedding and repopulation of monocytes, macrophages and DCs. | - |
dc.language | eng | - |
dc.relation.ispartof | European Journal of Immunology | - |
dc.subject | iRhom2 | - |
dc.subject | metalloprotease | - |
dc.subject | CSF1R | - |
dc.subject | myelopoiesis | - |
dc.subject | ADAM17 | - |
dc.title | iRhom2 regulates CSF1R cell surface expression and non-steady state myelopoiesis in mice | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1002/eji.201646482 | - |
dc.identifier.pmid | 27601030 | - |
dc.identifier.pmcid | PMC5149455 | - |
dc.identifier.scopus | eid_2-s2.0-84989285256 | - |
dc.identifier.volume | 46 | - |
dc.identifier.issue | 12 | - |
dc.identifier.spage | 2737 | - |
dc.identifier.epage | 2748 | - |
dc.identifier.eissn | 1521-4141 | - |
dc.identifier.isi | WOS:000392940400013 | - |
dc.identifier.issnl | 0014-2980 | - |