Gardner, PJ;
Liyanage, SE;
Cristante, E;
Sampson, RD;
Dick, AD;
Ali, RR;
Bainbridge, JW;
(2017)
Hypoxia inducible factors are dispensable for myeloid cell migration into the inflamed mouse eye.
Scientific Reports
, 7
, Article 40830. 10.1038/srep40830.
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Abstract
Hypoxia inducible factors (HIFs) are ubiquitously expressed transcription factors important for cell homeostasis during dynamic oxygen levels. Myeloid specific HIFs are crucial for aspects of myeloid cell function, including their ability to migrate into inflamed tissues during autoimmune disease. This contrasts with the concept that accumulation of myeloid cells at ischemic and hypoxic sites results from a lack of chemotactic responsiveness. Here we seek to address the role of HIFs in myeloid trafficking during inflammation in a mouse model of human uveitis. We show using mice with myeloid-specific Cre-deletion of HIFs that myeloid HIFs are dispensable for leukocyte migration into the inflamed eye. Myeloid-specific deletion of Hif1a, Epas1, or both together, had no impact on the number of myeloid cells migrating into the eye. Additionally, stabilization of HIF pathways via deletion of Vhl in myeloid cells had no impact on myeloid trafficking into the inflamed eye. Finally, we chemically induce hypoxemia via hemolytic anemia resulting in HIF stabilization within circulating leukocytes to demonstrate the dispensable role of HIFs in myeloid cell migration into the inflamed eye. These data suggest, contrary to previous reports, that HIF pathways in myeloid cells during inflammation and hypoxia are dispensable for myeloid cell tissue trafficking.
| Type: | Article |
|---|---|
| Title: | Hypoxia inducible factors are dispensable for myeloid cell migration into the inflamed mouse eye |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/srep40830 |
| Publisher version: | http://dx.doi.org/10.1038/srep40830 |
| Language: | English |
| Additional information: | Copyright © The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1537360 |
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