Increased autophagy contributes to the inflammatory phenotype of juvenile idiopathic arthritis synovial fluid T cells

Rheumatology (Oxford). 2017 Oct 1;56(10):1694-1699. doi: 10.1093/rheumatology/kex227.


Objectives: JIA is an autoimmune disease involving disturbed T-cell homeostasis, marked by highly activated effector T cells. Autophagy, a lysosomal degradation pathway, is crucial for maintaining cellular homeostasis by regulating the survival, differentiation and function of a large variety of cells, including T cells. The aim of this study was to examine the rate of autophagy in JIA T cells and to investigate the effect of inhibition of autophagy on the inflammatory phenotype of JIA T cells.

Methods: Autophagy-related gene expression was analysed in CD4+ T cells from the SF of JIA patients and healthy controls using RNA sequencing. Autophagy was measured by flow cytometry and western blot. The effect of inhibition of autophagy, using HCQ, on the cellular activation status was analysed using flow cytometry and multiplex immunoassay.

Results: Autophagy was increased in T cells derived from the site of inflammation compared with cells from the peripheral blood of patients and healthy controls. This increase in autophagy was not induced by JIA SF, but is more likely to be the result of increased cellular activation. Inhibition of autophagy reduced proliferation, cytokine production and activation marker expression of JIA SF-derived CD4+ T cells.

Conclusion: These data indicate that autophagy is increased in JIA SF-derived T cells and that targeting autophagy could be a promising therapeutic strategy to restore the disrupted T-cell homeostasis in JIA.

Keywords: T cells; autoimmune diseases; autoimmunity; autophagy; juvenile idiopathic arthritis; synovial fluid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Arthritis, Juvenile / immunology*
  • Autophagy / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / physiology*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Flow Cytometry
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Synovial Fluid / cytology*
  • Young Adult