RT Journal Article
SR Electronic
T1 Absence of MHC-II expression by lymph node stromal cells results in autoimmunity
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201800164
DO 10.26508/lsa.201800164
VO 1
IS 6
A1 Juan Dubrot
A1 Fernanda V Duraes
A1 Guillaume Harlé
A1 Anjalie Schlaeppi
A1 Dale Brighouse
A1 Natacha Madelon
A1 Christine Göpfert
A1 Nadine Stokar-Regenscheit
A1 Hans Acha-Orbea
A1 Walter Reith
A1 Monique Gannagé
A1 Stephanie Hugues
YR 2018
UL https://www.life-science-alliance.org/content/1/6/e201800164.abstract
AB 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.