Interleukin-23 deficiency alters thymic selection in lupus-prone mice

Lupus. 2019 Jul;28(8):1007-1012. doi: 10.1177/0961203319854804. Epub 2019 Jun 5.

Abstract

We have previously reported that IL-23 receptor deficiency in MRL.lpr mice ameliorates lupus by altering the balance of pro- and anti-inflammatory cytokines in secondary lymphoid organs. As IL-23 may also impact thymic selection, we evaluated the effect of IL-23 on thymic T cell development in lupus-prone mice. We generated IL-23p19-deficient MRL.lpr mice and harvested their thymus at 8 weeks of age. We found that the late stage double negative DN4 population was increased in IL-23p19-/- MRL.lpr mice when compared to IL-23p19+/+ MRL.lpr mice. Despite this, mature thymocytes (CD24-TCRβ+) were decreased by more than 50% in the IL-23p19-deficient mice versus wild-type controls. This was associated with a decrease in the generation of CD8+ T cells, possibly through downregulation of the IL-7 receptor. CD8+ T cells were not only fewer in numbers but also had decreased expression of the migration-related receptors CD44 and CD62L in the thymus and spleens of IL-23p19-deficient versus wild-type mice. We propose that IL-23 promotes the development of lupus-like autoimmunity not only through T cell polarization and cytokine production in the peripheral lymphoid organs but also by influencing T cell thymic development.

Keywords: Interleukin-23; MRL.; systemic lupus erythematosus; thymus.

MeSH terms

  • Animals
  • Autoantibodies / immunology
  • B-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Down-Regulation
  • Interleukin-23 Subunit p19 / genetics*
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / physiopathology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred MRL lpr
  • Mice, Knockout
  • Spleen / immunology
  • Thymus Gland / cytology
  • Thymus Gland / immunology*

Substances

  • Autoantibodies
  • Il23a protein, mouse
  • Interleukin-23 Subunit p19