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Title

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

Authors
Göpfert, Christine
Stokar-Regenscheit, Nadine
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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
PMID: 30584641
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Article (Published version) (2 MB) - public document Free access
Structures
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
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(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

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Deposited on : 2019-10-31

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