title: IL-22R Ligands IL-20, IL-22, and IL-24 Promote Wound Healing in Diabetic db/db Mice.
abstract: Diabetic foot ulcers (DFU) are one of the major complications in type II diabetes patients and can result in amputation and morbidity. Although multiple approaches are used clinically to help wound closure, many patients still lack adequate treatment. Here we show that IL-20 subfamily cytokines are upregulated during normal wound healing. While there is a redundant role for each individual cytokine in this subfamily in wound healing, mice deficient in IL-22R, the common receptor chain for IL-20, IL-22, and IL-24, display a significant delay in wound healing. Furthermore, IL-20, IL-22 and IL-24 are all able to promote wound healing in type II diabetic db/db mice. Mechanistically, when compared to other growth factors such as VEGF and PDGF that accelerate wound healing in this model, IL-22 uniquely induced genes involved in reepithelialization, tissue remodeling and innate host defense mechanisms from wounded skin. Interestingly, IL-22 treatment showed superior efficacy compared to PDGF or VEGF in an infectious diabetic wound model. Taken together, our data suggest that IL-20 subfamily cytokines, particularly IL-20, IL-22, and IL-24, might provide therapeutic benefit for patients with DFU.
authors.affiliation: Department of Biomedical Imaging, Genentech, South San Francisco, California, United States of America.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Kolumam
authors.affiliation: Department of Immunology, Genentech, South San Francisco, California, United States of America.
authors.forename: Xiumin
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Immunology, Genentech, South San Francisco, California, United States of America.
authors.forename: Wyne P
authors.initials: WP
authors.lastname: Lee
authors.affiliation: Department of Bioinformatics and Computational Biology, Genentech, South San Francisco, California, United States of America.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Hackney
authors.affiliation: Department of Molecular Biology, Genentech, South San Francisco, California, United States of America.
authors.forename: Jose
authors.initials: J
authors.lastname: Zavala-Solorio
authors.affiliation: Department of Biomedical Imaging, Genentech, South San Francisco, California, United States of America.
authors.forename: Vineela
authors.initials: V
authors.lastname: Gandham
authors.affiliation: Department of Safety Assessment Pathology, Genentech, South San Francisco, California, United States of America.
authors.forename: Dimitry M
authors.initials: DM
authors.lastname: Danilenko
authors.affiliation: Department of Early Clinical Development, Genentech, South San Francisco, California, United States of America.
authors.forename: Puneet
authors.initials: P
authors.lastname: Arora
authors.affiliation: Department of Immunology, Genentech, South San Francisco, California, United States of America.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Immunology, Genentech, South San Francisco, California, United States of America.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ouyang
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics* / Q000628:therapy; D017719:Diabetic Foot / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D005786:Gene Expression Regulation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage; D007378:Interleukins / Q000008:administration & dosage / Q000235:genetics*; D008024:Ligands; D051379:Mice; D016688:Mice, Inbred NOD; D018123:Receptors, Interleukin / Q000235:genetics*; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics*; D014946:Wound Infection / Q000235:genetics / Q000628:therapy; D000097043:Interleukin-22; D000099180:Interleukin-24
chemical_list: D007141:Immunoglobulin Fc Fragments; D007378:Interleukins; D008024:Ligands; D018123:Receptors, Interleukin; D000097043:Interleukin-22; D000099180:Interleukin-24; C415369:interleukin-22 receptor; C422042:interleukin 20