Premium
Interleukin‐23 regulates interleukin‐17 expression in wounds, and its inhibition accelerates diabetic wound healing through the alteration of macrophage polarization
Author(s) -
Lee James,
Rodero Mathieu Paul,
Patel Jatin,
Moi Davide,
Mazzieri Roberta,
Khosrotehrani Kiarash
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201700773r
Subject(s) - wound healing , macrophage polarization , m2 macrophage , inflammation , medicine , interleukin 17 , immunology , interleukin , interleukin 23 , interleukin 10 , macrophage , cytokine , biology , in vitro , biochemistry
Inflammation is a critical phase in the healing of skin wounds. Excessive inflammation and inflammatory macrophages are known to cause impaired wound closure and outcome. This prompted us to test the role of IL‐23 in IL‐17 expression and in modulating wound inflammation and macrophage polarization. Full‐thickness wounds (4 × 6 mm) were created on the dorsal surface of multiple genetically modified mouse models. Obese diabetic mouse wounds were treated with anti‐IL‐17A, anti‐IL‐23, or isotype‐matched antibodies. We found IL‐23‐ but not IL‐12‐deficient mice displayed significantly reduced IL‐17 expression in wounds. This was rescued by delivery of recombinant IL‐23. IL‐23‐ and IL‐17‐deficient mice showed a significant increase in noninflammatory macrophages. Obese diabetic mice treated with anti‐IL‐17A and anti‐IL‐23p19 blocking antibodies had significantly improved wound reepithelialization. Similarly, IL‐17 −/− obese mice had accelerated wound closure, resulting in reduced iNOS expression and inflammatory macrophages while maintaining prohealing CD206 and lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE1)‐expressing macrophages. This study highlights the importance of the IL‐17 pathway in wound closure offering new possibilities of therapeutic intervention in chronic wounds.— Lee, J., Rodero, M. P., Patel, J., Moi, D., Mazzieri, R., Khosrotehrani, K. Interleukin‐23 regulates interleukin‐17 expression in wounds, and its inhibition accelerates diabetic wound healing through the alteration of macrophage polarization. FASEB J. 32, 2086–2094 (2018). www.fasebj.org