作者: Patrick Möhnle , Stefanie V. Schütz , Verena van der Heide , Max Hübner , Benjamin Luchting
关键词:
摘要: T-cell functions must be tightly controlled to keep the balance between vital proinflammatory activity and detrimental overactivation. MicroRNA-146a (miR-146a) has been identified as a key negative regulator of responses in mice. Its role human T cells its relevance inflammatory disease, however, remains poorly defined. In this study, we have characterized miR-146a-driven pathways primary cells. Our results identify miR-146a critical gatekeeper Th1-cell differentiation processes acting via molecular mechanisms not uncovered so far. MiR-146a targets protein kinase C epsilon (PRKCe), which is part functional complex consisting PRKCe signal transducer activator transcription 4 (STAT4). Within complex, phosphorylates STAT4, turn capable promoting CD4+ lymphocytes. addition, observed that sepsis patients had reduced levels an increased expression initial hyperinflammatory phase disease. Collectively, our potent inhibitor suggest dysregulation contributes pathogenesis sepsis.