RESUMO
Rearrangement of the actin cytoskeleton is critical for cytotoxic and immunoregulatory functions as well as migration of natural killer (NK) cells. However, dynamic reorganization of actin is a complex process, which remains largely unknown. Here, we investigated the role of the protein Cereblon (CRBN), an E3 ubiquitin ligase complex co-receptor and the primary target of the immunomodulatory drugs, in NK cells. We observed that CRBN partially colocalizes with F-actin in chemokine-treated NK cells and is recruited to the immunological synapse, thus suggesting a role for this protein in cytoskeleton reorganization. Accordingly, silencing of CRBN in NK cells results in a reduced cytotoxicity that correlates with a defect in conjugate and lytic synapse formation. Moreover, CRBN depletion significantly impairs the ability of NK cells to migrate and reduces the enhancing effect of lenalidomide on NK cell migration. Finally, we provided evidence that CRBN is required for activation of the small GTPase Rac1, a critical mediator of cytoskeleton dynamics. Indeed, in CRBN-depleted NK cells, chemokine-mediated or target cell-mediated Rac1 activation is significantly reduced. Altogether our data identify a critical role for CRBN in regulating NK cell functions and suggest that this protein may mediate the stimulatory effect of lenalidomide on NK cells.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/imunologia , Movimento Celular/imunologia , Citotoxicidade Imunológica/imunologia , Células Matadoras Naturais/imunologia , Ubiquitina-Proteína Ligases/imunologia , Proteínas rac1 de Ligação ao GTP/imunologia , Movimento Celular/efeitos dos fármacos , Citotoxicidade Imunológica/efeitos dos fármacos , Humanos , Agentes de Imunomodulação/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Lenalidomida/farmacologiaRESUMO
Delirium is a highly relevant complication of surgical interventions. Current research indicates that despite increased awareness for delirium, it is often overlooked. We implemented an AI-based tool to monitor delirium in cardiac surgery patients in our specialist clinic. This appears to be a promising approach to improve detection of delirium, especially for underrecognized forms and in peripheral wards without intensive screening. We present a case in which the AI identified delirium, confirmed by our routine screening and specialist evaluation.