AI Article Synopsis
- The study identifies ubiquitin-specific protease USP8 as a key regulatory component in T cell signaling and its interaction with Gads and 14-3-3β.
- USP8 is crucial for thymocyte maturation and the upregulation of the IL-7Rα gene by the transcription factor Foxo1.
- Mice deficient in USP8 in T cells develop colitis due to disrupted T cell balance, suggesting that USP8 plays a significant role in immune regulation.
Article Abstract
The modification of proteins by ubiquitin has a major role in cells of the immune system and is counteracted by various deubiquitinating enzymes (DUBs) with poorly defined functions. Here we identified the ubiquitin-specific protease USP8 as a regulatory component of the T cell antigen receptor (TCR) signalosome that interacted with the adaptor Gads and the regulatory molecule 14-3-3β. Caspase-dependent processing of USP8 occurred after stimulation of the TCR. T cell-specific deletion of USP8 in mice revealed that USP8 was essential for thymocyte maturation and upregulation of the gene encoding the cytokine receptor IL-7Rα mediated by the transcription factor Foxo1. Mice with T cell-specific USP8 deficiency developed colitis that was promoted by disturbed T cell homeostasis, a predominance of CD8(+) γδ T cells in the intestine and impaired regulatory T cell function. Collectively, our data reveal an unexpected role for USP8 as an immunomodulatory DUB in T cells.
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| http://dx.doi.org/10.1038/ni.3230 | DOI Listing |
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