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miR-20a Inhibits TCR-Mediated Signaling and Cytokine Production in Human Naïve CD4(+) T Cells

Upon TCR stimulation by peptide-MHC complexes, CD4(+) T cells undergo activation and proliferation. This process will ultimately culminate in T-cell differentiation and the acquisition of effector functions. The production of specific cytokines by differentiated CD4(+) T cells is crucial for the gen...

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Detalles Bibliográficos
Autores principales: Reddycherla, Amarendra V., Meinert, Ines, Reinhold, Annegret, Reinhold, Dirk, Schraven, Burkhart, Simeoni, Luca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401545/
https://www.ncbi.nlm.nih.gov/pubmed/25884400
http://dx.doi.org/10.1371/journal.pone.0125311
Descripción
Sumario:Upon TCR stimulation by peptide-MHC complexes, CD4(+) T cells undergo activation and proliferation. This process will ultimately culminate in T-cell differentiation and the acquisition of effector functions. The production of specific cytokines by differentiated CD4(+) T cells is crucial for the generation of the appropriate immune response. Altered CD4(+) T-cell activation and cytokine production result in chronic inflammatory conditions and autoimmune disorders. miRNAs have been shown to be important regulators of T-cell biology. In this study, we have focused our investigation on miR-20a, a member of the miR-17-92 cluster, whose expression is decreased in patients suffering from multiple sclerosis. We have found that miR-20a is rapidly induced upon TCR-triggering in primary human naïve CD4(+) T cells and that its transcription is regulated in a Erk-, NF-κB-, and Ca(++)-dependent manner. We have further shown that overexpression of miR-20a inhibits TCR-mediated signaling but not the proliferation of primary human naïve CD4(+) T cells. However, miR-20a overexpression strongly suppresses IL-10 secretion and moderately decreases IL-2, IL-6 and IL8 production, which are crucial regulators of inflammatory responses. Our study suggests that miR-20a is a new player in the regulation of TCR signaling strength and cytokine production.