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Protein Phosphatase 1α and Cofilin Regulate Nuclear Translocation of NF-κB and Promote Expression of the Anti-Inflammatory Cytokine Interleukin-10 by T Cells.

dc.contributor.author Shenolikar, Shirish
dc.contributor.author Wabnitz, Guido H
dc.contributor.author Kirchgessner, Henning
dc.contributor.author Jahraus, Beate
dc.contributor.author Umansky, Ludmila
dc.contributor.author Samstag, Yvonne
dc.date.accessioned 2019-03-01T23:42:22Z
dc.date.available 2019-03-01T23:42:22Z
dc.date.issued 2018-11
dc.identifier MCB.00041-18
dc.identifier.issn 0270-7306
dc.identifier.issn 1098-5549
dc.identifier.uri https://hdl.handle.net/10161/18122
dc.description.abstract While several protein serine/threonine kinases control cytokine production by T cells, the roles of serine/threonine phosphatases are largely unexplored. Here, we analyzed the involvement of protein phosphatase 1α (PP1α) in cytokine synthesis following costimulation of primary human T cells. Small interfering RNA (siRNA)-mediated knockdown of PP1α (PP1KD) or expression of a dominant negative PP1α (D95N-PP1) drastically diminished interleukin-10 (IL-10) production. Focusing on a key transcriptional activator of human IL-10, we demonstrate that nuclear translocation of NF-κB was significantly inhibited in PP1KD or D95N-PP1 cells. Interestingly, knockdown of cofilin, a known substrate of PP1 containing a nuclear localization signal, also prevented nuclear accumulation of NF-κB. Expression of a constitutively active nonphosphorylatable S3A-cofilin in D95N-PP1 cells restored nuclear translocation of NF-κB and IL-10 expression. Subpopulation analysis revealed that defective nuclear translocation of NF-κB was most prominent in CD4+ CD45RA- CXCR3- T cells that included IL-10-producing TH2 cells. Together these findings reveal novel functions for PP1α and its substrate cofilin in T cells namely the regulation of the nuclear translocation of NF-κB and promotion of IL-10 production. These data suggest that stimulation of PP1α could limit the overwhelming immune responses seen in chronic inflammatory diseases.
dc.language eng
dc.publisher American Society for Microbiology
dc.relation.ispartof Molecular and cellular biology
dc.relation.isversionof 10.1128/mcb.00041-18
dc.subject T-cell activation
dc.subject cytokines
dc.subject phosphatase
dc.title Protein Phosphatase 1α and Cofilin Regulate Nuclear Translocation of NF-κB and Promote Expression of the Anti-Inflammatory Cytokine Interleukin-10 by T Cells.
dc.type Journal article
dc.date.updated 2019-03-01T23:42:12Z
pubs.issue 22
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Psychiatry & Behavioral Sciences, Translational Neuroscience
pubs.organisational-group Psychiatry & Behavioral Sciences
pubs.organisational-group Clinical Science Departments
pubs.publication-status Published
pubs.volume 38
duke.contributor.orcid Shenolikar, Shirish|0000-0003-0540-6328


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