Absence of MHC-II expression by lymph node stromal cells results in autoimmunity.
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BORIS DOI
Date of Publication
December 17, 2018
Publication Type
Article
Division/Institute
Author
Dubrot, Juan | |
Duraes, Fernanda V | |
Harlé, Guillaume | |
Schlaeppi, Anjalie | |
Brighouse, Dale | |
Madelon, Natacha | |
Acha-Orbea, Hans | |
Reith, Walter | |
Gannagé, Monique | |
Hugues, Stephanie |
Series
Life science alliance
ISSN or ISBN (if monograph)
2575-1077
Publisher
EMBO Press
Language
English
Publisher DOI
PubMed ID
30584641
Description
How lymph node stromal cells (LNSCs) shape peripheral T-cell responses remains unclear. We have previously demonstrated that murine LNSCs, lymphatic endothelial cells (LECs), blood endothelial cells (BECs), and fibroblastic reticular cells (FRCs) use the IFN-γ-inducible promoter IV (pIV) of the MHC class II (MHCII) transactivator CIITA to express MHCII. Here, we show that aging mice (>1 yr old) in which MHCII is abrogated in LNSCs by the selective deletion of pIV exhibit a significant T-cell dysregulation in LNs, including defective Treg and increased effector CD4 and CD8 T-cell frequencies, resulting in enhanced peripheral organ T-cell infiltration and autoantibody production. The proliferation of LN-Tregs interacting with LECs increases following MHCII up-regulation by LECs upon aging or after exposure to IFN-γ, this effect being abolished in mice in which LECs lack MHCII. Overall, our work underpins the importance of LNSCs, particularly LECs, in supporting Tregs and T-cell tolerance.
File(s)
File | File Type | Format | Size | License | Publisher/Copright statement | Content | |
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e201800164.full.pdf | text | Adobe PDF | 2 MB | Attribution (CC BY 4.0) | published |