In vivo generation of collagen specific Tregs with AAV8 suppresses autoimmune responses and arthritis in DBA1 mice through IL10 production

Sci Rep. 2021 Sep 14;11(1):18204. doi: 10.1038/s41598-021-97739-w.

Abstract

Available therapeutics for autoimmune disorders focused on mitigating symptoms, rather than treating the cause of the disorder. A novel approach using adeno-associated virus (AAV) could restore tolerance to the autoimmune targets and provide a permanent treatment for autoimmune diseases. Here, we evaluated the ability of collagen II T-cell epitopes packaged in adeno-associated virus serotype 8 (AAV-8) vectors to reduce pathogenic cellular and humoral responses against collagen and to mitigate the disease in the collagen-induced arthritis mouse model. The cytokines and immune cells involved in the immune suppression were also investigated. Mice treated with AAV-8 containing collagen II T-cell epitopes demonstrated a significant reduction in the arthritis symptoms, pathogenic collagen specific antibody and T cell responses. The AAV-8 mediated immune suppression was mediated by increased interleukin-10 expression and regulatory T cells expansion. Altogether, this study strengthens the notion that AAV vectors are promising candidates for the treatment of autoimmune diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / therapy*
  • Autoantibodies / immunology
  • Cells, Cultured
  • Collagen Type II / immunology
  • Dependovirus / genetics
  • Epitopes / immunology
  • Female
  • HEK293 Cells
  • Humans
  • Immunosuppression Therapy / methods*
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Mice
  • Mice, Inbred DBA
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Autoantibodies
  • Collagen Type II
  • Epitopes
  • Interleukin-10