In:
Nature Communications, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2020-05-12)
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.
Type of Medium:
Online Resource
ISSN:
2041-1723
DOI:
10.1038/s41467-020-16081-3
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2020
detail.hit.zdb_id:
2553671-0
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