| First Author | Zhang Y | Year | 2020 |
| Journal | J Exp Med | Volume | 217 |
| Issue | 5 | PubMed ID | 32069354 |
| Mgi Jnum | J:289911 | Mgi Id | MGI:6432585 |
| Doi | 10.1084/jem.20182218 | Citation | Zhang Y, et al. (2020) USP22 controls iNKT immunity through MED1 suppression of histone H2A monoubiquitination. J Exp Med 217(5) |
| abstractText | The ubiquitin pathway has been shown to regulate iNKT cell immunity, but the deubiquitinase involved in this process has not been identified. Herein we found that ubiquitin-specific peptidase 22 (USP22) is highly expressed in iNKT cells during their early developmental stage 1. USP22 deficiency blocked the transition from stage 1 to 2 during iNKT cell development in a cell-intrinsic manner. USP22 suppression also diminishes iNKT17 and iNKT1 differentiation but favors iNKT2 polarization without altering conventional T cell activation and differentiation. USP22 interacts with the Mediator complex subunit 1 (MED1), a transcription coactivator involved in iNKT cell development. Interestingly, while interacting with MED1, USP22 does not function as a deubiquitinase to suppress MED1 ubiquitination for its stabilization. Instead, USP22 enhances MED1 functions for IL-2Rbeta and T-bet gene expression through deubiquitinating histone H2A but not H2B monoubiquitination. Therefore, our study revealed USP22-mediated histone H2A deubiquitination fine-tunes MED1 transcriptional activation as a previously unappreciated molecular mechanism to control iNKT development and functions. |
