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

Dubrot, Juan; Duraes, Fernanda V; Harlé, Guillaume; Schlaeppi, Anjalie; Brighouse, Dale; Madelon, Natacha; Göpfert, Christine; Stokar von Neuforn, Nadine; Acha-Orbea, Hans; Reith, Walter; Gannagé, Monique; Hugues, Stephanie (2018). Absence of MHC-II expression by lymph node stromal cells results in autoimmunity. Life science alliance, 1(6), e201800164. EMBO Press 10.26508/lsa.201800164

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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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