Absence of MHC-II expression by lymph node stromal cells results in autoimmunity.

Details

Ressource 1Download: e201800164.full.pdf (2046.61 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_8398D98F5515
Type
Article: article from journal or magazin.
Collection
Publications
Title
Absence of MHC-II expression by lymph node stromal cells results in autoimmunity.
Journal
Life Science Alliance
Author(s)
Dubrot J., Duraes F.V., Harlé G., Schlaeppi A., Brighouse D., Madelon N., Göpfert C., Stokar-Regenscheit N., Acha-Orbea H., Reith W., Gannagé M., Hugues S.
ISSN
2575-1077 (Electronic)
ISSN-L
2575-1077
Publication state
Published
Issued date
2018
Peer-reviewed
Oui
Volume
1
Number
6
Pages
e201800164
Language
english
Abstract
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 <sup>+</sup> and CD8 <sup>+</sup> 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.
Pubmed
Open Access
Yes
Create date
20/01/2019 15:59
Last modification date
20/08/2019 14:43
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