Abstract

IL-27, as a pleiotropic cytokine, promotes the differentiation of naïve T cells to Th1, while suppressing Th2 and Th17 differentiation in the periphery. However, the role of IL-27 in the thymocyte development remains unknown. Here we showed that IL-27 was highly expressed in thymic plasmacytoid dendritic cells (pDCs) while its receptor expression was mainly detected in CD4+ single-positive (SP) thymocytes. Deletion of the p28 subunit in DCs resulted in a reduction of the most mature Qa-2+ subsets of CD4+ SP T cells. This defect was rescued by intrathymic administration of exogenous IL-27. In vitro differentiation assay further demonstrated that IL-27 alone was able to drive the maturation of the newly generated 6C10+CD69+CD4+ SP cells into Qa-2+ cells. Collectively, this study has revealed an important role of thymic DCs-derived IL-27 in the regulation of the phenotypic maturation of CD4+ SP thymocytes.

Highlights

  • Thymus is the main site of T lymphopoiesis

  • DC-specific deletion of the gene encoding IL-27p28 resulted in the reduction of Qa-2+ CD4 SP T cells in the thymus, supporting that it is critically involved in the phenotypic maturation of CD4+ SP thymocytes

  • To investigate the potential role of IL-27 in thymocyte development, we first examined the expression of IL-27 and its receptors in various thymic cell populations

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Summary

Introduction

On the basis of CD4 and CD8 expression, the process of thymocyte development can be divided into three major stages, double-negative (DN), double-positive (DP) and single-positive (SP)[1,2,3]. Both CD4 SP and CD8 SP thymocytes exhibit significant heterogeneity in phenotype, featured by the expression of 6C10, CD69 and heat-stable antigen (HSA) at the early stage and the acquisition of Qa-2 at the late stage[4,5,6,7,8]. DC-specific deletion of the gene encoding IL-27p28 resulted in the reduction of Qa-2+ CD4 SP T cells in the thymus, supporting that it is critically involved in the phenotypic maturation of CD4+ SP thymocytes

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