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Toll-like receptor signaling in thymic epithelium controls monocyte-derived dendritic cell recruitment and Treg generation by VoboÅil, MatouÅ¡; Brabec, TomáÅ¡; DobeÅ¡, Jan; Å plíchalová, Iva; BÅezina, JiÅí; Äepková, Adéla; DobeÅ¡ová, Martina; Aidarova, Aigerim; KubovÄiak, Jan; Tsyklauri, Oksana; Å tÄpánek, OndÅej; BeneÅ¡, Vladimír; SedláÄek, Radislav; Klein, Ludger; KoláÅ, Michal; Filipp, Dominik is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Toll-like receptor signaling in thymic epithelium controls monocyte-derived dendritic cell recruitment and Treg generation about?

The development of thymic regulatory T cells (Treg) is mediated by Aire-regulated self-antigen presentation on medullary thymic epithelial cells (mTECs) and dendritic cells (DCs), but the cooperation between these cells is still poorly understood. Here we show that signaling through Toll-like receptors (TLR) expressed on mTECs regulates the production of specific chemokines and other genes associated with post-Aire mTEC development. Using single-cell RNA-sequencing, we identify a new thymic CD14^+^Sirpα^+^ population of monocyte-derived dendritic cells (CD14^+^moDC) that are enriched in the thymic medulla and effectively acquire mTEC-derived antigens in response to the above chemokines. Consistently, the cellularity of CD14^+^moDC is diminished in mice with MyD88-deficient TECs, in which the frequency and functionality of thymic CD25^+^Foxp3^+^ Tregs are decreased, leading to aggravated mouse experimental colitis. Thus, our findings describe a TLR-dependent function of mTECs for the recruitment of CD14^+^moDC, the generation of Tregs, and thereby the establishment of central tolerance.

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Author

VoboÅil, MatouÅ¡; Brabec, TomáÅ¡; DobeÅ¡, Jan; Å plíchalová, Iva; BÅezina, JiÅí; Äepková, Adéla; DobeÅ¡ová, Martina; Aidarova, Aigerim; KubovÄiak, Jan; Tsyklauri, Oksana; Å tÄpánek, OndÅej; BeneÅ¡, Vladimír; SedláÄek, Radislav; Klein, Ludger; KoláÅ, Michal; Filipp, Dominik

Publisher

Nature Publishing Group; Springer Science and Business Media LLC; [London]: Nature Publishing Group, 2010-; Society for Mining, Metallurgy and Exploration Inc.; Research Square (ISSN 2041-1723)

Published

2020

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)