Interleukin-28A enhances autoimmune disease in a retinal autoimmunity model

Cytokine. 2014 Dec;70(2):179-84. doi: 10.1016/j.cyto.2014.07.252. Epub 2014 Aug 17.

Abstract

Interleukin-28A (IL-28A), a member of type III interferons (IFN-λs), promotes antiviral, antitumor and immune responses. However, its ability to regulate autoimmune diseases is poorly understood. In this study, we examined the effect of IL-28A on retinal antigen-induced experimental autoimmune uveoretinitis (EAU), a mouse model of human T-cell-mediated autoimmune eye disease. We found that administration of IL-28A enhanced EAU scores and autoimmune response parameters including delayed-type hypersensitivity (DTH), Ag-specific T cell proliferation and the production of Ag-specific IL-17 and IFN-γ in the priming phase. The effect of IL-28A was abrogated by administration of a neutralizing antibody against IL-28A. Our results suggest that IL-28A is capable of exacerbating a T-cell-mediated autoimmune disease. Thus, targeting IL-28A may provide a new therapeutic approach to T cell-mediated autoimmune diseases such as uveitis.

Keywords: Autoimmune disease; Type III interferon; Uveitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antigens / immunology
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / pathology
  • Autoimmunity*
  • Disease Models, Animal
  • Dose-Response Relationship, Immunologic
  • Humans
  • Hypersensitivity, Delayed / immunology
  • Hypersensitivity, Delayed / pathology
  • Interferon-gamma / biosynthesis
  • Interleukin-17 / biosynthesis
  • Interleukins / genetics
  • Interleukins / immunology
  • Interleukins / metabolism*
  • Lymph Nodes / metabolism
  • Mice
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Retina / immunology*
  • Retina / pathology*

Substances

  • Antibodies
  • Antigens
  • IL28A protein, mouse
  • Interleukin-17
  • Interleukins
  • RNA, Messenger
  • Interferon-gamma