Dampened ERK signaling in hematopoietic progenitor cells in rheumatoid arthritis

Inés Colmegna, Sergey Pryshchep, Hisashi Oishi, Jörg J. Goronzy, Cornelia M. Weyand

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

In rheumatoid arthritis (RA), hematopoietic progenitor cells (HPC) have age-inappropriate telomeric shortening suggesting premature senescence and possible restriction of proliferative capacity. In response to hematopoietic growth factors RA-derived CD34 + HPC expanded significantly less than age-matched controls. Cell surface receptors for stem cell factor (SCF), Flt 3-Ligand, IL-3 and IL-6 were intact in RA HPC but the cells had lower transcript levels of cell cycle genes, compatible with insufficient signal strength in the ERK pathway. Cytokine-induced phosphorylation of ERK1/2 was diminished in RA HPC whereas phosphorylated STAT3 and STAT5 molecules accumulated to a similar extent as in controls. Confocal microscopy demonstrated that the membrane-proximal colocalization of K-Ras and B-Raf was less efficient in RA-derived CD34 + cells. Thus, hyporesponsiveness of RA HPC to growth factors results from dampening of the ERK signaling pathways; with a defect localized in the very early steps of the ERK signaling cascade.

Original languageEnglish (US)
Pages (from-to)73-82
Number of pages10
JournalClinical Immunology
Volume143
Issue number1
DOIs
StatePublished - Apr 2012

Keywords

  • CD34
  • ERK signaling
  • Hematopoietic progenitor cells
  • Rheumatoid arthritis
  • STAT signaling

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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