Journal article
iRhom2 regulates CSF1R cell surface expression and non-steady state myelopoiesis in mice
European journal of immunology, Vol.46(12), pp.2737-2748
12/2016
DOI: 10.1002/eji.201646482
PMCID: PMC5149455
PMID: 27601030
Abstract
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.
Details
- Title: Subtitle
- iRhom2 regulates CSF1R cell surface expression and non-steady state myelopoiesis in mice
- Creators
- Xiaoping Qing - Program in Inflammation and Autoimmunity, Hospital for Special Surgery, 535 East 71 St., New York, NY 10021, USALindsay Rogers - Centre for Blood Research, University of British Columbia, Vancouver, BC V6T 1Z3, CanadaArthur Mortha - Department of Oncological Sciences, Tisch Cancer Institute and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York City, New York 10029, USAYonit Lavin - Department of Oncological Sciences, Tisch Cancer Institute and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York City, New York 10029, USAPatricia Redecha - Program in Inflammation and Autoimmunity, Hospital for Special Surgery, 535 East 71 St., New York, NY 10021, USAPriya D Issuree - Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, NY 10021, USAThorsten Maretzky - Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, NY 10021, USAMiriam Merad - Department of Oncological Sciences, Tisch Cancer Institute and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York City, New York 10029, USADavid McIlwain - Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305Tak W Mak - Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Center, University Health Network, Toronto, ON, M5G 2M9, CanadaChristopher M Overall - Centre for Blood Research, University of British Columbia, Vancouver, BC V6T 1Z3, CanadaCarl P Blobel - Department of Physiology, Systems Biology and Biophysics, Weill Medical College of Cornell University, New York, New York 10021, USAJane E Salmon - Department of Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA
- Resource Type
- Journal article
- Publication Details
- European journal of immunology, Vol.46(12), pp.2737-2748
- DOI
- 10.1002/eji.201646482
- PMID
- 27601030
- PMCID
- PMC5149455
- ISSN
- 0014-2980
- eISSN
- 1521-4141
- Grant note
- R01 GM064750 / NIGMS NIH HHS R01 CA173861 / NCI NIH HHS R01 CA190400 / NCI NIH HHS
- Language
- English
- Date published
- 12/2016
- Academic Unit
- Infectious Diseases; Internal Medicine
- Record Identifier
- 9984094323902771
Metrics
32 Record Views