title: Reduced Il17a expression distinguishes a Ly6c(lo)MHCII(hi) macrophage population promoting wound healing.
abstract: Macrophages are the main components of inflammation during skin wound healing. They are critical in wound closure and in excessive inflammation, resulting in defective healing observed in chronic wounds. Given the heterogeneity of macrophage phenotypes and functions, we here hypothesized that different subpopulations of macrophages would have different and sometimes opposing effects on wound healing. Using multimarker flow cytometry and RNA expression array analyses on macrophage subpopulations from wound granulation tissue, we identified a Ly6c(lo)MHCII(hi) "noninflammatory" subset that increased both in absolute number and proportion during normal wound healing and was missing in Ob/Ob and MYD88-/- models of delayed healing. We also identified IL17 as the main cytokine distinguishing this population from proinflammatory macrophages and demonstrated that inhibition of IL17 by blocking Ab or in IL17A-/- mice accelerated normal and delayed healing. These findings dissect the complexity of the role and activity of the macrophages during wound inflammation and may contribute to the development of therapeutic approaches to restore healing in chronic wounds.
authors.affiliation: University of Queensland Centre for Clinical Research, Experimental Dermatology Group, Brisbane, Queensland, Australia.
authors.forename: Mathieu P
authors.initials: MP
authors.lastname: Rodero
authors.affiliation: University of Queensland Centre for Clinical Research, Experimental Dermatology Group, Brisbane, Queensland, Australia.
authors.forename: Samantha S
authors.initials: SS
authors.lastname: Hodgson
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Brett
authors.initials: B
authors.lastname: Hollier
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Inserm UMR-S 945, Paris, France; Service d'Immunologie, Groupe Hospitalier Pitié-Salpétrière, Assistance Public-Hôpitaux de Paris, Paris, France; Laboratory of Immunity and Infection, Université Pierre et Marie Curie (UPMC Univ Paris 06), Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Combadiere
authors.affiliation: University of Queensland Centre for Clinical Research, Experimental Dermatology Group, Brisbane, Queensland, Australia. Electronic address: k.khosrotehrani@uq.edu.au.
authors.forename: Kiarash
authors.initials: K
authors.lastname: Khosrotehrani
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000950:Antigens, Ly / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000473:pathology; D002454:Cell Differentiation; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics; D020738:Leptin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D023421:Models, Animal; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D000906:Antibodies; D000950:Antigens, Ly; D000949:Histocompatibility Antigens Class II; D020381:Interleukin-17; D020738:Leptin; C494192:Ly-6C antigen, mouse; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88