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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F20%3A00525579" target="_blank" >RIV/68378050:_____/20:00525579 - isvavai.cz</a>

Result on the web

<a href="https://www.nature.com/articles/s41467-020-16081-3" target="_blank" >https://www.nature.com/articles/s41467-020-16081-3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-020-16081-3" target="_blank" >10.1038/s41467-020-16081-3</a>

Result language

angličtina

Original language name

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

Original language description

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(+)Sirp alpha (+) 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. Immune tolerance is mediated by the deletion of autoreactive T cells via medullary thymic epithelial cells (mTEC) and dendritic cells (DC), and by the induction of regulatory T cells (Treg). Here the authors show that mTEC receiving toll-like receptor signaling control the recruitment of CD14(+)Sirp alpha (+) DC population that is capable of inducing Treg for establishing tolerance.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30102 - Immunology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Nature Communications

ISSN

2041-1723

e-ISSN

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Volume of the periodical

11

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

16

Pages from-to

2361

UT code for WoS article

000537242500002

EID of the result in the Scopus database

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