title: Targeting the IL-17/IFN-γ axis as a potential new clinical therapy for type 1 diabetes.
abstract: Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing pancreatic beta cells. There is now mounting evidence that pro-inflammatory pathways, which are mediated by T cells that secrete IL-17 and IFN-γ, play a critical role in the loss of beta cells. These data suggest that blockade of T cells that secrete IL-17 and IFN-γ may halt or reverse disease in subjects with recent-onset T1D. Agents to facilitate this approach are currently in clinical use. Ustekinumab, a humanized monoclonal antibody that targets the shared p40 subunit of IL-12 and IL-23, has been used for the treatment of psoriasis, an indication for which it has proven to be safe and effective. In this review, we summarize the evidence that supports a combined pathogenic role of IL-17 and IFN-γ in the development of T1D, with the aim of providing a rationale for testing agents such as ustekinumab for the treatment of T1D.
authors.affiliation: Department of Dermatology and Skin Science, Faculty of Medicine, Child and Family Research Institute, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Marwaha
authors.affiliation: Department of Dermatology and Skin Science, Faculty of Medicine, Child and Family Research Institute, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Sara
authors.initials: S
authors.lastname: Tan
authors.affiliation: Department of Dermatology and Skin Science, Faculty of Medicine, Child and Family Research Institute, The University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: dutz@interchange.ubc.ca.
authors.forename: Jan P
authors.initials: JP
authors.lastname: Dutz
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology / Q000628:therapy*; D016503:Drug Delivery Systems; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D000069549:Ustekinumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D020381:Interleukin-17; D007371:Interferon-gamma; D000069549:Ustekinumab
keywords: Clinical trial; IFN-γ;; IL-17;; Stelara;; Type 1 diabetes;; Ustekinumab;