Targeting the IL-17/IFN-γ axis as a potential new clinical therapy for type 1 diabetes

Clin Immunol. 2014 Sep;154(1):84-9. doi: 10.1016/j.clim.2014.06.006. Epub 2014 Jun 16.

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.

Keywords: Clinical trial; IFN-γ;; IL-17;; Stelara;; Type 1 diabetes;; Ustekinumab;.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diabetes Mellitus, Type 1 / therapy*
  • Drug Delivery Systems*
  • Humans
  • Interferon-gamma / immunology*
  • Interleukin-17 / immunology*
  • T-Lymphocytes / immunology
  • Ustekinumab

Substances

  • Antibodies, Monoclonal, Humanized
  • Interleukin-17
  • Interferon-gamma
  • Ustekinumab