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

Area of Science:

• Immunology
• Autoimmunity
• T cell development

Background:

• Previous studies showed Interleukin-23 (IL-23) receptor deficiency ameliorates lupus in MRL.lpr mice by altering cytokine balance.
• The role of IL-23 in thymic T cell selection and its impact on lupus pathogenesis remained unclear.

Purpose of the Study:

• To investigate the effect of IL-23 on thymic T cell development in lupus-prone MRL.lpr mice.
• To determine if IL-23 influences T cell populations and their maturation within the thymus.

Main Methods:

• Generation of IL-23p19-deficient MRL.lpr mice.
• Analysis of thymic T cell populations at 8 weeks of age using flow cytometry.
• Assessment of T cell receptor (TCR) and surface marker expression (CD24, TCRβ, CD8, CD44, CD62L).

Main Results:

• Increased late-stage double negative (DN4) T cell population in IL-23p19-/- MRL.lpr mice.
• Significant decrease (>50%) in mature thymocytes (CD24-TCRβ+) in IL-23p19-deficient mice.
• Reduced generation of CD8+ T cells, potentially linked to IL-7 receptor downregulation.
• Diminished expression of CD44 and CD62L on CD8+ T cells in both thymus and spleen of deficient mice.

Conclusions:

• IL-23 influences T cell development within the thymus, impacting CD8+ T cell maturation and migration.
• IL-23 may promote lupus-like autoimmunity through both peripheral T cell polarization and central thymic T cell development.
• Targeting IL-23 could offer a therapeutic strategy for lupus by modulating T cell development.