TY - JOUR T1 - Absence of MHC-II expression by lymph node stromal cells results in autoimmunity JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201800164 VL - 1 IS - 6 SP - e201800164 AU - Juan Dubrot AU - Fernanda V Duraes AU - Guillaume Harlé AU - Anjalie Schlaeppi AU - Dale Brighouse AU - Natacha Madelon AU - Christine Göpfert AU - Nadine Stokar-Regenscheit AU - Hans Acha-Orbea AU - Walter Reith AU - Monique Gannagé AU - Stephanie Hugues Y1 - 2018/12/01 UR - https://www.life-science-alliance.org/content/1/6/e201800164.abstract N2 - 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. ER -