Foxa1 and Foxa2 in thymic epithelial cells (TEC) regulate medullary TEC and regulatory T-cell maturation

Article


Lau, Ching-In, Yánez, Diana C., Solanki, Anisha, Papaioannou, Eleftheria, Saldaña, J. and Crompton, Tessa 2018. Foxa1 and Foxa2 in thymic epithelial cells (TEC) regulate medullary TEC and regulatory T-cell maturation. Journal of Autoimmunity. 93, pp. 131-138.
AuthorsLau, Ching-In, Yánez, Diana C., Solanki, Anisha, Papaioannou, Eleftheria, Saldaña, J. and Crompton, Tessa
Abstract

The Foxa1 and Foxa2 transcription factors are essential for mouse development. Here we show that they are expressed in thymic epithelial cells (TEC) where they regulate TEC development and function, with important consequences for T-cell development. TEC are essential for T-cell differentiation, lineage decisions and repertoire selection. Conditional deletion of Foxa1 and Foxa2 from murine TEC led to a smaller thymus with a greater proportion of TEC and a greater ratio of medullary to cortical TEC. Cell-surface MHCI expression was increased on cortical TEC in the conditional Foxa1Foxa2 knockout thymus, and MHCII expression was reduced on both cortical and medullary TEC populations. These changes in TEC differentiation and MHC expression led to a significant reduction in thymocyte numbers, reduced positive selection of CD4+CD8+ cells to the CD4 lineage, and increased CD8 cell differentiation. Conditional deletion of Foxa1 and Foxa2 from TEC also caused an increase in the medullary TEC population, and increased expression of Aire, but lower cell surface MHCII expression on Aire-expressing mTEC, and increased production of regulatory T-cells. Thus, Foxa1 and Foxa2 in TEC promote positive selection of CD4SP T-cells and modulate regulatory T-cell production and activity, of importance to autoimmunity.

JournalJournal of Autoimmunity
Journal citation93, pp. 131-138
ISSN0896-8411
Year2018
PublisherElsevier for Academic Press
Publisher's version
License
Digital Object Identifier (DOI)doi:10.1016/j.jaut.2018.07.009
Web address (URL)https://doi.org/10.1016/j.jaut.2018.07.009
Publication dates
Online27 Jul 2018
PrintSep 2018
Publication process dates
Deposited09 Aug 2018
Accepted15 Jul 2018
Accepted15 Jul 2018
FunderMedical Research Council
Biotechnology and Biological Sciences Research Council
Great Ormond Street Hospital Charity
National Institute for Health Research Biomedical Research Centres
National Secretariat for Higher Education, Science, Technology and Innovation of Ecuador
Medical Research Council
Biotechnology and Biological Sciences Research Council
Great Ormond Street Hospital Charity
National Institute for Health Research Biomedical Research Centre
National Secretariat for Higher Education, Science, Technology and Innovation of Ecuador
Copyright information© 2018 The authors
LicenseCC BY 4.0
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