| First Author | Johansson K | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 10 | Pages | 113298 |
| PubMed ID | 37862171 | Mgi Jnum | J:342322 |
| Mgi Id | MGI:7548227 | Doi | 10.1016/j.celrep.2023.113298 |
| Citation | Johansson K, et al. (2023) An essential role for miR-15/16 in Treg suppression and restriction of proliferation. Cell Rep 42(10):113298 |
| abstractText | The miR-15/16 family targets a large network of genes in T cells to restrict their cell cycle, memory formation, and survival. Upon T cell activation, miR-15/16 are downregulated, allowing rapid expansion of differentiated effector T cells to mediate a sustained response. Here, we used conditional deletion of miR-15/16 in regulatory T cells (Tregs) to identify immune functions of the miR-15/16 family in T cells. miR-15/16 are indispensable to maintain peripheral tolerance by securing efficient suppression by a limited number of Tregs. miR-15/16 deficiency alters expression of critical Treg proteins and results in accumulation of functionally impaired FOXP3(lo)CD25(lo)CD127(hi) Tregs. Excessive proliferation in the absence of miR-15/16 shifts Treg fate and produces an effector Treg phenotype. These Tregs fail to control immune activation, leading to spontaneous multi-organ inflammation and increased allergic inflammation in a mouse model of asthma. Together, our results demonstrate that miR-15/16 expression in Tregs is essential to maintain immune tolerance. |
