Recombinant Adeno-Associated Virus Expressing Truncated IK Cytokine Diminishes the Symptoms of Inflammatory Arthritis

J Microbiol Biotechnol. 2017 Oct 28;27(10):1892-1895. doi: 10.4014/jmb.1705.05018.

Abstract

IK can downregulate interferon-gamma-induced major histocompatibility complex (MHC) class II expression through the MHC class II transactivator, which suggests that IK can inhibit the interactions between immune cells. We delivered adeno-associated virus serotype 2 (AAV2) encoding the genes for truncated IK (tIK) or green fluorescent protein (GFP) to DBA1/J mice via intravenous injection. Seven weeks after injection, collagen-induced arthritis was induced in the AAV2-treated mice. AAV2-tIK injection reduced the severity of arthritis and the percentage of pathogenic Th17 cells compared with AAV2-GFP injection. These results suggest a novel gene therapy strategy for treatment of inflammatory arthritis.

Keywords: Adeno-associated virus; gene therapy; inflammatory arthritis; rheumatoid arthritis; truncated IK.

MeSH terms

  • Animals
  • Ankle Joint / pathology
  • Anti-Inflammatory Agents / pharmacology*
  • Arthritis / drug therapy*
  • Arthritis / immunology*
  • Arthritis / pathology
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Dependovirus / genetics*
  • Dependovirus / immunology*
  • Disease Models, Animal
  • Gene Expression / immunology
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Green Fluorescent Proteins / genetics
  • HEK293 Cells
  • Humans
  • Immunohistochemistry
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred DBA
  • Recombinant Proteins / genetics
  • Recombinant Proteins / pharmacology*
  • Th17 Cells

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Ik protein, mouse
  • Recombinant Proteins
  • Green Fluorescent Proteins
  • Interferon-gamma