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

Article Article scientifique Article Absence of MHC-II expression by lymph node stromal cells results in autoimmunity eng 2018 author Dubrot Armendariz Juan 744966 author Do Valle Duraes Fernanda 733292 author Harle Guillaume 880027 author Schlaeppi Anjalie 751852 author Brighouse Dale 134767 author Madelon Natacha 780405 author Göpfert Christine author Stokar-Regenscheit Nadine author Acha-Orbea Hans author Reith Walter 25482 author Gannagé Monique 812150 author Hugues Stéphanie 663452 e201800164 10.26508/lsa.201800164 30584641 2575-1077 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. Dewey 616 Dewey 616.07 Swiss National Science Foundation The study of how plasmacytoid dendritic cells can be manipulated to control inflammatory and autoimmune diseases 152951 CH Careers Swiss National Science Foundation MHCII mediated Antigen-presentation by Lymph Node Stromal Cells in Autoimmunity and Cancer 166541 CH Project funding 137 Département de pathologie et immunologie 21F 56 Département de médecine 221 false 221 Groupe Reith Walter (pathologie et immunologie) 282 563 Pathologie et immunologie 906 Life Science Alliance 1 6 9f340196-53bc-4358-91ad-4873db642e56 Article (Published version) Public 2019_Dubrot_LSA.pdf 2093611 application/pdf CC BY openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique / Département de médecine

Title	Published in	Year	Views	Downloads

Absence of MHC-II expression by lymph node stromal cells results in autoimmunity	Life Science Alliance	2018	406	352
MHCII mediated antigen-presentation by lymph node stromal cells in autoimmunity and cancer		2016	120	19

Archive ouverte UNIGE

Schlaeppi, Anjalie