1. An essential role for miR-15/16 in Treg suppression and restriction of proliferation
- Author
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Kristina Johansson, John D. Gagnon, Simon K. Zhou, Marlys S. Fassett, Andrew W. Schroeder, Robin Kageyama, Rodriel A. Bautista, Hewlett Pham, Prescott G. Woodruff, and K. Mark Ansel
- Subjects
CP: Immunology ,Biology (General) ,QH301-705.5 - Abstract
Summary: 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.
- Published
- 2023
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