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
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 i...
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| Hauptverfasser: | , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
4 September 2018
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| In: |
Molecular and cellular biology
Year: 2018, Jahrgang: 38, Heft: 22 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/MCB.00041-18 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1128/MCB.00041-18
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| Verfasserangaben: | Guido H. Wabnitz, Henning Kirchgessner, Beate Jahraus, Ludmila Umansky, Shirish Shenolikar, Yvonne Samstag |
| Zusammenfassung: | 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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| Beschreibung: | Gesehen am 11.04.2019 |
| Beschreibung: | Online Resource |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/MCB.00041-18 |