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

Interleukin-23 deficiency alters thymic selection in lupus-prone mice.
Lupus. 2019 Jun 05;:961203319854804
Authors: Dai H, Kyttaris VC
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.
PMID: 31166866 [PubMed - as supplied by publisher]

Source: Lupus - June 4, 2019 Category: Rheumatology Authors: Dai H, Kyttaris VC Tags: Lupus Source Type: research