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

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Dubrot, Juan | Duraes, Fernanda | Harlé, Guillaume | Schlaeppi, Anjalie | Brighouse, Dale | Madelon, Natacha | Göpfert, Christine | Stokar-Regenscheit, Nadine | Acha-Orbea, Hans | Reith, Walter | Gannagé, Monique | Hugues, Stephanie

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International audience. 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.

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