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

Dubrot Armendariz, Juan; Do Valle Duraes, Fernanda; Harle, Guillaume; Schlaeppi, Anjalie; Brighouse, Dale; Madelon, Natacha; Göpfert, Christine; Stokar-Regenscheit, Nadine; Acha-Orbea, Hans; Reith, Walter; Gannagé, Monique; Hugues, Stéphanie

doi:10.26508/lsa.201800164

Advanced search

Browse by...

Deposit

Highlights

More informations

Title		Absence of MHC-II expression by lymph node stromal cells results in autoimmunity
Authors		Dubrot Armendariz, Juan Do Valle Duraes, Fernanda Harle, Guillaume Schlaeppi, Anjalie Brighouse, Dale Madelon, Natacha Göpfert, Christine Stokar-Regenscheit, Nadine Acha-Orbea, Hans Reith, Walter Gannagé, Monique Hugues, Stéphanie show all authors [1 - 12]
Published in		Life Science Alliance. 2018, vol. 1, no. 6, e201800164
Abstract		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.
Identifiers		DOI: 10.26508/lsa.201800164 PMID: 30584641
Full text		Article (Published version) (2 MB) - Free access
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Research groups		Groupe Reith Walter (pathologie et immunologie) (282) Pathologie et immunologie (906)
Projects		Swiss National Science Foundation: PP00P3_152951 Swiss National Science Foundation: 310030_166541
Citation (ISO format)		DUBROT ARMENDARIZ, Juan et al. Absence of MHC-II expression by lymph node stromal cells results in autoimmunity. In: Life Science Alliance, 2018, vol. 1, n° 6, p. e201800164. doi: 10.26508/lsa.201800164 https://archive-ouverte.unige.ch/unige:125387