Background/Purpose: 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 also may also impact thymic selection, we evaluated the effect of IL-23 on thymic selection in lupus prone mice.

Methods: We generated MRL.lpr mice that lack the IL-23p19 subunit by backcrossing with a B6.IL23p19 deficient mice for 11 generations. Thymic tissue was harvested from 6-8 week old mice and used for flow cytometry.

Results: IL23p19-/-MRL.lpr mice had decreased proteinuria when compared to wild type mice. IL-23p19 deficiency resulted in reduced expression of both IL-7Ra and RORγt in thymocytes. This was associated with reduction of CD3 and TCRβ expression on thymocytes by 35% and 50% respectively. Overall IL-23p19-/-MRL.lpr mice had as much as 50% reduction in cells that underwent positive selection. On the contrary IL23p19 deficiency did not affect T cells lineage commitment, nor changed CCR7 expression, a major determinant of cortex-medulla intra-thymic migration. The resulting, post positive and negative selection, T lymphocytes in IL23p19 deficient mice displayed an immature phenotype as measured by CD44 and CD62L expression in both thymus and spleens.

Conclusion: IL-23 deficiency in lupus prone mice strongly influences thymic selection resulting in T lymphocytes exiting the thymus with an immature phenotype. We propose that IL-23 not only promotes the development of lupus like autoimmunity through T cell polarization and cytokine production in the peripheral lymphoid organs but also by influencing T cell selection in the thymus.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/il23-deficiency-alters-thymic-selection-in-lupus-prone-mice/