| First Author | Chen SW | Year | 2025 |
| Journal | Cell Rep | Volume | 44 |
| Issue | 1 | Pages | 115161 |
| PubMed ID | 39786996 | Mgi Jnum | J:367700 |
| Mgi Id | MGI:7864734 | Doi | 10.1016/j.celrep.2024.115161 |
| Citation | Chen SW, et al. (2025) ECM29/proteasome-mediated self-antigen generation by CNS-resident neuroglia promotes regulatory T cell activation. Cell Rep 44(1):115161 |
| abstractText | Proteasomes generate antigenic peptides presented on cell surfaces-a process that, in neuroglia, is highly responsive to external stimuli. However, the function of the self-antigens presented by CNS parenchymal cells remains unclear. Here, we report that the fidelity of neuroglial self-antigens is crucial to suppress encephalitogenic T cell responses by elevating regulatory T (Treg) cell populations. We demonstrate that loss of the proteasome adaptor protein Ecm29 alters the efficacy and accuracy of antigen generation. Inducible oligodendroglia- or microglia-conditional Ecm29 knockout mice exhibit higher susceptibility to experimental autoimmune encephalomyelitis (EAE) than control counterparts do, coincident with reduced Treg cell populations in the spinal cord. Immunopeptidome profiling identifies self-antigens that modulate myelin-reactive T cell responses. Intraspinal adeno-associated virus (AAV)/Olig001-mediated expression of the self-antigen NDUFA1p ameliorates EAE and expands NDUFA1p-recognizing CD103(+)CD8(+)CD122(+) Treg cells. Thus, Ecm29/proteasome-controlled, neuroglia-derived self-antigens modulate CNS immune tolerance. |
