Toll-like receptor signaling in thymic epithelium controls monocyte-derived dendritic cell recruitment and Treg generation.

Abstract:

: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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Vobořil M,Brabec T,Dobeš J,Šplíchalová I,Březina J,Čepková A,Dobešová M,Aidarova A,Kubovčiak J,Tsyklauri O,Štěpánek O,Beneš V,Sedláček R,Klein L,Kolář M,Filipp D

doi

10.1038/s41467-020-16081-3

subject

Has Abstract

pub_date

2020-05-12 00:00:00

pages

2361

issue

1

issn

2041-1723

pii

10.1038/s41467-020-16081-3

journal_volume

11

pub_type

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