| First Author | Michelson DA | Year | 2022 |
| Journal | Proc Natl Acad Sci U S A | Volume | 119 |
| Issue | 48 | Pages | e2215474119 |
| PubMed ID | 36409920 | Mgi Jnum | J:335884 |
| Mgi Id | MGI:7485713 | Doi | 10.1073/pnas.2215474119 |
| Citation | Michelson DA, et al. (2022) CTLA-4 on thymic epithelial cells complements Aire for T cell central tolerance. Proc Natl Acad Sci U S A 119(48):e2215474119 |
| abstractText | Medullary thymic epithelial cells (mTECs) are essential for the establishment of T cell central tolerance. The transcription factor Aire plays a key role in this process, but other factors remain understudied. We found that a small population of mTECs expressed the coinhibitory receptor cytotoxic T lymphocyte-associated protein 4 (CTLA-4). These CTLA-4(+) cells were detectable in perinates, peaked around young adulthood and expanded sixfold in the absence of Aire. Single-cell transcriptomics revealed CTLA-4(+) mTECs to express a distinct gene signature encoding molecules associated with antigen presentation and interferon-gamma signaling. Mice conditionally lacking CTLA-4 in thymic epithelial cells had no major immunological deficiencies but displayed a mildly increased inflammatory tone and a partial defect in the generation of Foxp3(+)CD4(+) regulatory T cells. Consequently, these mice developed modest levels of autoantibodies and lymphocytic infiltration of peripheral tissues. Thus, CTLA-4 expression in mTECs complements Aire to establish T cell central tolerance. |
