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

Published inLife Science Alliance, vol. 1, no. 6, e201800164
Publication date2018
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.

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
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ISSN of the journal2575-1077
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