Aire controls the recirculation of murine Foxp3+ regulatory T-cells back to the thymus

Research output: Contribution to journalArticle

Authors

  • Nicholas I McCarthy
  • Sonia M Parnell
  • Andrea J White

Colleges, School and Institutes

External organisations

  • Institute for Immunology and Immunotherapy, College of Medical and Dental Sciences, Medical School, University of Birmingham, Birmingham, B15 2TT, England.

Abstract

In the thymus, medullary thymic epithelial cells (mTEC) determine the fate of newly selected CD4+ and CD8+ single positive (SP) thymocytes. For example, mTEC expression of Aire controls intrathymic self-antigen availability for negative selection. Interestingly, alterations in both Foxp3+ Regulatory T-cells (T-Reg) and conventional SP thymocytes in Aire-/- mice suggest additional, yet poorly understood, roles for Aire during intrathymic T-cell development. To examine this, we analysed thymocytes from Aire-/- mice using Rag2GFP and Foxp3 expression, and a recently described CD69/MHCI subset definition of post-selection CD4+ conventional thymocytes. We show that while Aire is dispensable for de novo generation of conventional αβT-cells, it plays a key role in controlling the intrathymic T-Reg pool size. Surprisingly, this decline in intrathymic T-Reg in Aire-/- mice maps to a reduction in mature recirculating Rag2GFP- T-Reg that express CCR6 and re-enter the thymus from the periphery. Furthermore, we show mTEC expression of the CCR6 ligand CCL20 is reduced in Aire-/- mice, and that CCR6 is required for T-Reg recirculation back to the thymus. Collectively, our study re-defines requirements for late stage intrathymic αβT-cell development, and demonstrates that Aire controls a CCR6-CCL20 axis that determines the developmental makeup of the intrathymic T-Reg pool. This article is protected by copyright. All rights reserved.

Details

Original languageEnglish
Pages (from-to)844-854
JournalEuropean Journal of Immunology
Volume48
Issue number5
Early online date29 Dec 2017
Publication statusPublished - May 2018

Keywords

  • Thymopoiesis, Thymus, Thymic epithelium, Thymic selection, Thymocyte