59 research outputs found

    The ubiquitin-editing enzyme A20 controls NK cell homeostasis through regulation of mTOR activity and TNF

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    The ubiquitin-editing enzyme A20 is a well-known regulator of immune cell function and homeostasis. In addition, A20 protects cells from death in an ill-defined manner. While most studies focus on its role in the TNF-receptor complex, we here identify a novel component in the A20-mediated decision between life and death. Loss of A20 in NK cells led to spontaneous NK cell death and severe NK cell lymphopenia. The few remaining NK cells showed an immature, hyperactivated phenotype, hallmarked by the basal release of cytokines and cytotoxic molecules. NK-A20−/− cells were hypersensitive to TNF-induced cell death and could be rescued, at least partially, by a combined deficiency with TNF. Unexpectedly, rapamycin, a wellestablished inhibitor of mTOR, also strongly protected NK-A20−/− cells from death, and further studies revealed that A20 restricts mTOR activation in NK cells. This study therefore maps A20 as a crucial regulator of mTOR signaling and underscores the need for a tightly balanced mTOR pathway in NK cell homeostasis

    Comparison of thymic histology with response to thymectomy in myasthenia gravis

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    Fifty-four thymus glands removed surgically from patients with myasthenia gravis were examined using an accurate morphometric technique and the data compared with the response to thymectomy. There is a tendency for patients with relatively unreactive thymus glands to obtain a better result from thymectomy but this is not statistically significant
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