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 language | English (US) |
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Pages (from-to) | 73-82 |
Number of pages | 10 |
Journal | Clinical Immunology |
Volume | 143 |
Issue number | 1 |
DOIs | |
State | Published - Apr 2012 |
Keywords
- CD34
- ERK signaling
- Hematopoietic progenitor cells
- Rheumatoid arthritis
- STAT signaling
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology