

![]() |
Absence of MHC-II expression by lymph node stromal cells results in autoimmunity |
|
Authors | ![]() | |
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 | |
Full text | ||
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 | |
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 |