title: Reduction of ARNT in myeloid cells causes immune suppression and delayed wound healing.
abstract: Aryl hydrocarbon receptor nuclear translocator (ARNT) is a transcription factor that binds to partners to mediate responses to environmental signals. To investigate its role in the innate immune system, floxed ARNT mice were bred with lysozyme M-Cre recombinase animals to generate lysozyme M-ARNT (LAR) mice with reduced ARNT expression. Myeloid cells of LAR mice had altered mRNA expression and delayed wound healing. Interestingly, when the animals were rendered diabetic, the difference in wound healing between the LAR mice 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 (DFO) improves wound healing by increasing hypoxia-inducible factors, 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 strategy to improve wound healing.
authors.affiliation: Diabetes and Transcription Factors Group, Department of Immunology and Inflammation, Garvan Institute of Medical Research, Sydney, New South Wales, Australia; Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia;
authors.forename: Christopher
authors.initials: C
authors.lastname: Scott
authors.affiliation: Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia;
authors.forename: James
authors.initials: J
authors.lastname: Bonner
authors.affiliation: Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia;
authors.forename: Danqing
authors.initials: D
authors.lastname: Min
authors.affiliation: St. George Clinical School, St. George Hospital, Kogarah, New South Wales, Australia; Department of Biomedical Engineering, University of Sydney, Sydney, New South Wales, Australia;
authors.forename: Philip
authors.initials: P
authors.lastname: Boughton
authors.affiliation: Diabetes and Transcription Factors Group, Department of Immunology and Inflammation, Garvan Institute of Medical Research, Sydney, New South Wales, Australia;
authors.forename: Rebecca
authors.initials: R
authors.lastname: Stokes
authors.affiliation: Diabetes and Transcription Factors Group, Department of Immunology and Inflammation, Garvan Institute of Medical Research, Sydney, New South Wales, Australia;
authors.forename: Kuan Minn
authors.initials: KM
authors.lastname: Cha
authors.affiliation: Department of Immunology and Inflammation, Garvan Institute of Medical Research, Sydney, New South Wales, Australia;
authors.forename: Stacey N
authors.initials: SN
authors.lastname: Walters
authors.affiliation: Department of Biochemistry, University of Lausanne, Lausanne, Switzerland;
authors.forename: Kendle
authors.initials: K
authors.lastname: Maslowski
authors.affiliation: Liver Immunology, Centenary Institute, Sydney, New South Wales, Australia;
authors.forename: Frederic
authors.initials: F
authors.lastname: Sierro
authors.affiliation: Department of Immunology and Inflammation, Garvan Institute of Medical Research, Sydney, New South Wales, Australia;
authors.forename: Shane T
authors.initials: ST
authors.lastname: Grey
authors.affiliation: Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia; Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia;
authors.forename: Stephen
authors.initials: S
authors.lastname: Twigg
authors.affiliation: Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia; Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia;
authors.forename: Susan
authors.initials: S
authors.lastname: McLennan
authors.affiliation: Diabetes and Transcription Factors Group, Department of Immunology and Inflammation, Garvan Institute of Medical Research, Sydney, New South Wales, Australia; Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia; St. Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia; and Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, New South Wales, Australia jenny.gunton@sydney.edu.au j.gunton@garvan.org.au.
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Gunton
mesh_terms: D000368:Aged; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D003872:Dermatitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D048909:Diabetes Complications / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006085:Graft Survival; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D016867:Immunocompromised Host / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism; D019426:Integrases / Q000235:genetics; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009113:Muramidase / Q000235:genetics; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016038:Skin Transplantation; D013997:Time Factors; D023001:Transplantation Tolerance / Q000235:genetics; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics
chemical_list: C497396:ARNT protein, human; C497397:Arnt protein, mouse; D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; C045073:Cre recombinase; D019426:Integrases; D009113:Muramidase; D003676:Deferoxamine
keywords: aryl hydrocarbon receptor nuclear translocator; deferoxamine; hypoxia-inducible factor-1α