Deficiency of N-myristoylation reveals calcineurin activity as regulator of IFN-γ-producing γδ T cells. Issue 4 (6th January 2017)

• Record Type: Journal Article
• Authors: Rampoldi, Francesca; Brunk, Fabian; Bonrouhi, Mahnaz; Federico, Giuseppina; Krunic, Damir; Porubsky, Stefan; Gröne, Hermann-Josef; Popovic, Zoran V
• Is Part Of: Journal of leukocyte biology. Volume 101:Issue 4(2017)
• Page Start: 1005
• Page End: 1014
• Publication Date: 2017-01-06
• Subjects: CD27+ γδ T cells -- Calcineurin-Nfatc pathway -- IL-17A -- IFN-γ; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.1A0616-264R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Calcineurin-Nfatc pathway promotes development and function of IFNγ-producing γδ T cells. Abstract: γδ T cell subsets can be characterized, in part, by their secretion of select proinflammatory cytokines. The molecular mechanisms driving the diverse fates of γδ T cells have not been elucidated. We have previously shown that the attachment of myristic acid to the N-terminal glycine of proteins, termed N-myristoylation, is essential for αβ T cell development and activation. Here, we explore the potential role of this lipid modification on the activation of γδ T cells. In the absence of N-myristoylation, the CD27 + γδ T cell subset was dominantly affected. The cells produced high levels of IFN-γ upon stimulation. In addition, they were more sensitive to inhibition of the CaN-Nfat pathway than were γδ T cells with myristoylated CaN. N-Myristoylation was found to modulate activity of phosphatase CaN, a regulator of Nfat. In summary, the CaN–Nfat pathway regulates development and function of IFN-γ-producing γδ T cells, and its balanced activity is strongly dependent on CaN N-myristoylation.