Enhanced expression of mRNA for FLT3 in bone marrow CD34+ cells in rheumatoid arthritis

抄録

Objective: We have recently demonstrated that the generation of pre-plasmacytoid dendritic cells (pre-pDC) from bone marrow (BM) CD34+ cells is increased in rheumatoid arthritis (RA) compared with osteoarthritis (OA) in correlation with the degree of synovial proliferation. It has been shown that FLT3 ligand promotes the differentiation of pDC through its interaction with FLT3 on pDC precursors. We explored the expression of FLT3 mRNA in BM CD34+ cells in RA to delineate the mechanism for their abnormal differentiation into pre-pDC.
Methods: CD34+ cells were purified from BM samples obtained from 46 RA patients and from 29 OA patients during joint operations via aspiration from the iliac crest. The expression of FLT3 mRNA was examined by quantitative RT-PCR.
Results: The expression of FLT3 mRNA was significantly higher in RA BM CD34+ cells than in OA BM CD34+ cells (FLT3/β-actin: [0.686 ± 0.152] × 10^-3 and [0.252 ± 0.053] × 10^-3 [mean ± SEM], respectively; p=0.0269). FLT3 mRNA expression was not correlated with serum CRP or with administration of methotrexate or oral steroid. Finally, TNF-α did not enhance FLT3 mRNA expression, but rather decreased it, in BM CD34+ cells from normal individuals.
Conclusions: These results indicate that FLT3 mRNA expression is upregulated in RA BM CD34+ cells independently of the systemic inflammation or treatment regimens. The data therefore suggest that abnormal FLT3 mRNA expression in BM CD34+ cells might lead to the expansion of immature pDC in RA BM, supporting the enhanced output of pDC into the inflamed synovium in RA.