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

• Published in: Life science alliance Vol. 1; no. 6; p. e201800164
• Main Authors: Dubrot, Juan, Duraes, Fernanda V, Harlé, Guillaume, Schlaeppi, Anjalie, Brighouse, Dale, Madelon, Natacha, Göpfert, Christine, Stokar-Regenscheit, Nadine, Acha-Orbea, Hans, Reith, Walter, Gannagé, Monique, Hugues, Stephanie
• Format: Journal Article
• Language: English
• Published: United States Life Science Alliance LLC 01.12.2018
• Subjects: Adaptive immunology; Immunology; Life Sciences
• ISSN: 2575-1077; 2575-1077
• DOI: 10.26508/lsa.201800164

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.