Abstract
Roquin proteins preclude spontaneous T cell activation and aberrant differentiation of T follicular helper (Tfh) or T helper 17 (Th17) cells. Here we showed that deletion of Roquin-encoding alleles specifically in regulatory T (Treg) cells also caused the activation of conventional T cells. Roquin-deficient Treg cells downregulated CD25, acquired a follicular Treg (Tfr) cell phenotype, and suppressed germinal center reactions but could not protect from colitis. Roquin inhibited the PI3K-mTOR signaling pathway by upregulation of Pten through interfering with miR-17 similar to 92 binding to an overlapping cis-element in the Pten 3' UTR, and downregulated the Foxo1-specific E3 ubiquitin ligase Itch. Loss of Roquin enhanced Akt-mTOR signaling and protein synthesis, whereas inhibition of PI3K or mTOR in Roquin-deficient T cells corrected enhanced Tfh and Th17 or reduced iTreg cell differentiation. Thereby, Roquin-mediated control of PI3K-mTOR signaling prevents autoimmunity by restraining activation and differentiation of conventional T cells and specialization of Treg cells.
| Item Type: | Journal article |
|---|---|
| Faculties: | Medicine |
| Research Centers: | Center for Integrated Protein Science Munich (CIPSM) |
| Subjects: | 600 Technology > 610 Medicine and health 500 Science > 540 Chemistry |
| ISSN: | 1074-7613 |
| Language: | English |
| Item ID: | 50005 |
| Date Deposited: | 14. Jun 2018, 09:42 |
| Last Modified: | 04. Nov 2020, 13:27 |
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