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

Jennifer E Cowan, Song Baik, Nicholas I McCarthy, Sonia M Parnell, Andrea J White, William E Jenkinson, Graham Anderson

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)
144 Downloads (Pure)

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.

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

Keywords

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

Fingerprint

Dive into the research topics of 'Aire controls the recirculation of murine Foxp3+ regulatory T-cells back to the thymus'. Together they form a unique fingerprint.

Cite this