Protein phosphatase 1α and cofilin regulate nuclear translocation of NF-[kappa]B and promote expression of the anti-inflammatory cytokine interleukin-10 by T cells

• Verfasst von: Wabnitz, Guido H. [VerfasserIn]
• Verfasst von: Kirchgessner, Henning [VerfasserIn]
• Verfasst von: Jahraus, Beate [VerfasserIn]
• Verfasst von: Umansky, Ludmila [VerfasserIn]
• Verfasst von: Samstag, Yvonne [VerfasserIn]
• Titel: Protein phosphatase 1α and cofilin regulate nuclear translocation of NF-[kappa]B and promote expression of the anti-inflammatory cytokine interleukin-10 by T cells
• Verf.angabe: Guido H. Wabnitz, Henning Kirchgessner, Beate Jahraus, Ludmila Umansky, Shirish Shenolikar, Yvonne Samstag
• E-Jahr: 2018
• Jahr: 4 September 2018
• Umfang: 17 S.
• Fussnoten: Gesehen am 11.04.2019
• Titel Quelle: Enthalten in: Molecular and cellular biology
• Ort Quelle: Washington, DC : Soc., 1981
• Jahr Quelle: 2018
• Band/Heft Quelle: 38(2018,17) Artikel-Nummer e00041-18, 17 Seiten
• ISSN Quelle: 1098-5549
• DOI: doi:10.1128/MCB.00041-18
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: cytokines
• Sach-SW: phosphatase
• Sach-SW: T-cell activation
• K10plus-PPN: 1663120196

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.