MicroRNA‐146a controls Th1‐cell differentiation of human CD4+ T lymphocytes by targeting PRKCε. Issue 1 (27th November 2014)

• Record Type: Journal Article
• Authors: Möhnle, Patrick; Schütz, Stefanie V.; van der Heide, Verena; Hübner, Max; Luchting, Benjamin; Sedlbauer, Julia; Limbeck, Elisabeth; Hinske, Ludwig C.; Briegel, Josef; Kreth, Simone
• Is Part Of: European journal of immunology. Volume 45:Issue 1(2015)
• Page Start: 260
• Page End: 272
• Publication Date: 2014-11-27
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201444667
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 T‐cell responses in mice. Its role in human T cells and its relevance to human inflammatory disease, however, remains poorly defined. In this study, we have characterized miR‐146a‐driven pathways in primary human T cells. Our results identify miR‐146a as a critical gatekeeper of Th1‐cell differentiation processes acting via molecular mechanisms not uncovered so far. MiR‐146a targets protein kinase C epsilon (PRKCε), which is part of a functional complex consisting of PRKCε and signal transducer and activator of transcription 4 (STAT4). Within this complex, PRKCε phosphorylates STAT4, which in turn is capable of promoting Th1‐cell differentiation processes in human CD4⁺ T lymphocytes. In addition, we observed that T cells of sepsis patients had reduced levels of miR‐146a and an increased PRKCε expression in the initial hyperinflammatory phase of the disease. Collectively, our results identify miR‐146a as a potent inhibitor of Th1‐cell differentiation in human T cells and suggest that dysregulation of miR‐146a contributes to the pathogenesis of sepsis.</p> </abstract>