Reduction of ARNT (Aryl hydrocarbon Receptor Nuclear Translocator) in myeloid cells causes immune suppression and delayed wound healing
Aryl hydrocarbon receptor nuclear translocator (ARNT) is a transcription factor which binds to partners to mediate responses to environmental signals. To investigate its role in the innate immune system, floxed ARNT mice were bred with LysM-Cre animals to generate LysM-ARNT (LAR) mice with reduced ARNT expression. Myeloid cells of LAR mice had altered mRNA expression and delayed wound healing. Interestingly, when made diabetic, the difference in wound healing between the LAR and their littermate controls was no longer present, suggesting that decreased myeloid cell ARNT function may be an important factor in impaired wound healing in diabetes. Deferoxamine improves wound healing by increasing hypoxia-inducible factors (HIFs), which require ARNT for function. DFO was not effective in wounds of LAR mice, again suggesting that myeloid cells are important for normal wound healing, and for the full benefit of DFO. These findings suggest that myeloid ARNT is important for immune function and wound healing. Increasing ARNT, and more specifically myeloid ARNT may be a therapeutic target to improve wound healing.
|ISBN||1522-1563 (Electronic) 0363-6143 (Linking)|
|Authors||Scott, C.; Bonner, J.; Min, D.; Boughton, P.; Stokes, R.; Cha, K. M.; Walters, S. N.; Masolowski, K.; Sierro, F.; Grey, S. T.; Twigg, S.; McLennan, S.; Gunton, J. E.;|
|Publisher Name||AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/24990649|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/12436|