| First Author | Dubrot J | Year | 2018 |
| Journal | Life Sci Alliance | Volume | 1 |
| Issue | 6 | Pages | e201800164 |
| PubMed ID | 30584641 | Mgi Jnum | J:287934 |
| Mgi Id | MGI:6391777 | Doi | 10.26508/lsa.201800164 |
| Citation | Dubrot J, et al. (2018) Absence of MHC-II expression by lymph node stromal cells results in autoimmunity. Life Sci Alliance 1(6):e201800164 |
| abstractText | 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-gamma-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-gamma, 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. |
