Absence of MHC-II expression by lymph node stromal cells results in autoimmunity.
Juan DubrotFernanda V DuraesGuillaume HarléAnjalie SchlaeppiDale BrighouseNatacha MadelonChristine GoepfertNadine Stokar-RegenscheitHans Acha-OrbeaWalter ReithMonique GannagéStephanie HuguesPublished in: Life science alliance (2018)
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.
Keyphrases
- lymph node
- endothelial cells
- dendritic cells
- high fat diet induced
- sentinel lymph node
- neoadjuvant chemotherapy
- immune response
- induced apoptosis
- poor prognosis
- dna methylation
- signaling pathway
- regulatory t cells
- gene expression
- transcription factor
- type diabetes
- chemotherapy induced
- cell cycle arrest
- adipose tissue
- protein kinase
- oxidative stress
- cell death
- skeletal muscle
- nk cells
- locally advanced
- type iii
- celiac disease