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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.

Publication ,  Journal Article
Wabnitz, GH; Kirchgessner, H; Jahraus, B; Umansky, L; Shenolikar, S; Samstag, Y
Published in: Mol Cell Biol
November 15, 2018

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.

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Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

November 15, 2018

Volume

38

Issue

22

Location

United States

Related Subject Headings

  • Th2 Cells
  • Protein Transport
  • Protein Phosphatase 1
  • NF-kappa B
  • Interleukin-10
  • Inflammation
  • Immunity
  • Humans
  • Developmental Biology
  • Cytokines
 

Citation

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Wabnitz, G. H., Kirchgessner, H., Jahraus, B., Umansky, L., Shenolikar, S., & Samstag, Y. (2018). Protein Phosphatase 1α and Cofilin Regulate Nuclear Translocation of NF-κB and Promote Expression of the Anti-Inflammatory Cytokine Interleukin-10 by T Cells. Mol Cell Biol, 38(22). https://doi.org/10.1128/MCB.00041-18
Wabnitz, Guido H., Henning Kirchgessner, Beate Jahraus, Ludmila Umansky, Shirish Shenolikar, and Yvonne Samstag. “Protein Phosphatase 1α and Cofilin Regulate Nuclear Translocation of NF-κB and Promote Expression of the Anti-Inflammatory Cytokine Interleukin-10 by T Cells.Mol Cell Biol 38, no. 22 (November 15, 2018). https://doi.org/10.1128/MCB.00041-18.
Wabnitz GH, Kirchgessner H, Jahraus B, Umansky L, Shenolikar S, Samstag Y. Protein Phosphatase 1α and Cofilin Regulate Nuclear Translocation of NF-κB and Promote Expression of the Anti-Inflammatory Cytokine Interleukin-10 by T Cells. Mol Cell Biol. 2018 Nov 15;38(22).
Wabnitz, Guido H., et al. “Protein Phosphatase 1α and Cofilin Regulate Nuclear Translocation of NF-κB and Promote Expression of the Anti-Inflammatory Cytokine Interleukin-10 by T Cells.Mol Cell Biol, vol. 38, no. 22, Nov. 2018. Pubmed, doi:10.1128/MCB.00041-18.
Wabnitz GH, Kirchgessner H, Jahraus B, Umansky L, Shenolikar S, Samstag Y. Protein Phosphatase 1α and Cofilin Regulate Nuclear Translocation of NF-κB and Promote Expression of the Anti-Inflammatory Cytokine Interleukin-10 by T Cells. Mol Cell Biol. 2018 Nov 15;38(22).

Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

November 15, 2018

Volume

38

Issue

22

Location

United States

Related Subject Headings

  • Th2 Cells
  • Protein Transport
  • Protein Phosphatase 1
  • NF-kappa B
  • Interleukin-10
  • Inflammation
  • Immunity
  • Humans
  • Developmental Biology
  • Cytokines