%0 Journal Article %A Juan Dubrot %A Fernanda V Duraes %A Guillaume Harlé %A Anjalie Schlaeppi %A Dale Brighouse %A Natacha Madelon %A Christine Göpfert %A Nadine Stokar-Regenscheit %A Hans Acha-Orbea %A Walter Reith %A Monique Gannagé %A Stephanie Hugues %T Absence of MHC-II expression by lymph node stromal cells results in autoimmunity %D 2018 %R 10.26508/lsa.201800164 %J Life Science Alliance %P e201800164 %V 1 %N 6 %X 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. %U https://www.life-science-alliance.org/content/lsa/1/6/e201800164.full.pdf