| First Author | Morimoto J | Year | 2022 |
| Journal | Cell Rep | Volume | 38 |
| Issue | 7 | Pages | 110384 |
| PubMed ID | 35172142 | Mgi Jnum | J:320898 |
| Mgi Id | MGI:6874536 | Doi | 10.1016/j.celrep.2022.110384 |
| Citation | Morimoto J, et al. (2022) Aire suppresses CTLA-4 expression from the thymic stroma to control autoimmunity. Cell Rep 38(7):110384 |
| abstractText | Impaired production of thymic regulatory T cells (Tregs) is implicated in the development of Aire-dependent autoimmunity. Because Tregs require agonistic T cell receptor stimuli by self-antigens to develop, reduced expression of self-antigens from medullary thymic epithelial cells (mTECs) has been considered to play a major role in the reduced Treg production in Aire deficiency. Here, we show that mTECs abnormally express co-inhibitory receptor CTLA-4 if Aire is non-functional. Upon binding with CD80/CD86 ligands expressed on thymic dendritic cells (DCs), the ectopically expressed CTLA-4 from Aire-deficient mTECs removes the CD80/CD86 ligands from the DCs. This attenuates the ability of DCs to provide co-stimulatory signals and to present self-antigens transferred from mTECs, both of which are required for Treg production. Accordingly, impaired production of Tregs and organ-specific autoimmunity in Aire-deficient mice are rescued by the depletion of CTLA-4 expression from mTECs. Our studies illuminate the significance of mTEC-DC interaction coordinated by Aire for the establishment of thymic tolerance. |
