An essential role for miR-15/16 in Treg suppression and restriction of proliferation
In: Cell Reports, Jg. 42 (2023-10-01), Heft 10
Online
academicJournal
- 113298
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 FOXP3loCD25loCD127hi 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.
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An essential role for miR-15/16 in Treg suppression and restriction of proliferation
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Autor/in / Beteiligte Person: | Johansson, Kristina ; Gagnon, John D ; Zhou, Simon K ; Fassett, Marlys S ; Schroeder, Andrew W ; Kageyama, Robin ; Bautista, Rodriel A ; Pham, Hewlett ; Woodruff, Prescott G ; Ansel, K Mark |
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Zeitschrift: | Cell Reports, Jg. 42 (2023-10-01), Heft 10 |
Veröffentlichung: | eScholarship, University of California, 2023 |
Medientyp: | academicJournal |
Umfang: | 113298 |
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