Dubrot, JuanJuanDubrotDuraes, Fernanda VFernanda VDuraesHarlé, GuillaumeGuillaumeHarléSchlaeppi, AnjalieAnjalieSchlaeppiBrighouse, DaleDaleBrighouseMadelon, NatachaNatachaMadelonGöpfert, ChristineChristineGöpfertStokar von Neuforn, NadineNadineStokar von NeufornAcha-Orbea, HansHansAcha-OrbeaReith, WalterWalterReithGannagé, MoniqueMoniqueGannagéHugues, StephanieStephanieHugues2025-01-082025-01-082018-12-17https://boris-portal.unibe.ch/handle/20.500.12422/200473How 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.en600 - Technology::630 - Agriculture500 - Science::570 - Life sciences; biology600 - Technology::610 - Medicine & healtharticle10.7892/boris.1275363058464110.26508/lsa.201800164