IL-12 family cytokines play crucial roles in T cell immune responses in the peripheral which regulate the inflammatory and tolerance. Interestingly, previous reports have demonstrated that IL-12 and IL-23 have supportive effect in the thymic negative selection and regulatory T cell generation. However, their roles in the TCR repertoire diversity and subsequent effect on the peripheral immunity is unclear. In this study, we used IL-12p35 knockout and IL-23p19 knockdown NOD mouse model to address this issue. We first found increased thymocyte numbers in IL-12p35 knockout and IL-23p19 knockdown NOD mouse. Then we used thymus transplantation and bone marrow chimera model to investigate the effects of these cytokine on TCR repertoire distribution and autoimmune phenotype. The NOD-RAG1 -/- mice which received IL-23p19 knockdown thymus displayed increased susceptibility to autoimmunity. Interestingly, T cells derived from IL-12p35 knockout thymus showed increased IFN-g and decreased IL-17 production in peripheral and inflammatory lesion. Our data suggested that IL-12 and IL-23 have supportive role in the central tolerance and defect of these cytokines in the thymus could leads to autoimmunity.
Date:
2019-10
Relation:
European Journal of Immunology. 2019 Oct;49(S3):377.
