ABSTRACT
To date, multiple genetic susceptible genes/loci associated with rheumatoid arthritis (RA) have been identified and confirmed through large-scale genetic association studies and genome-wide association study (GWAS). However, the heritability of RA could be not fully explained by these genetic factors, and gene-gene interaction might account for part of the missing heritability. Indeed, genetic interaction study is a critical research direction in the field of genetic epidemiology of RA, and these studies have provided novel insights into the genetic basis and pathogenesis of RA. Additionally, these studies have also provided scientific reference for risk prediction and prevention of RA. This review is aimed to present a summary of recent progress in genetic interaction study of RA, thus implicate further research in this field.
ABSTRACT
Objective:To investigate the effect of IL-34 on the phenotype of monocyte derived dendritic cells in RA,and to speculate the role of IL-34 in the differentiation of myeloid dendritic cells.Methods:The peripheral blood of RA patients was collected to harvest PBMC by Ficoll density gradient centrifugation and cultured for 4h.Adherent cells were stimulated with GM-CSF+IL-4,IL-4, IL-4+IL-34 for 3 days,and then the expression of CD83,CD86 and CD14 was tested by flow cytometry.In addition,the cells stimulated by GM-CSF and IL-4 were added by TNF-α with or without IL-34 for another four days.The expression of CD83,CD86 and/or CD14 was detected by flow cytometry.Results:(1)The expression of CD83 and CD86 on immature DC induced by IL-34+IL-4 was upregulated compared with IL-4 alone(P<0.01),but no difference of the CD14 levels between the two groups(P>0.05).The levels of CD86 and CD14 induced by IL-34+IL-4 were slightly decreased compared with GM-CSF+IL-4 stimulation(P<0.05),but no difference of CD83 expression between the two groups(P>0.05).(2)The expression of CD83 and CD86 stimulated by GM-CSF+IL-4+IL-34 was lower than the GM-CSF+IL-4+TNF-α group(P<0.05),but no difference compared with GM-CSF+IL-4 group(P>0.05). (3)The CD83 expression induced by GM-CSF+IL-4+TNF-α+IL-34 was lower than GM-CSF+IL-4+TNF-α group(P<0.05),but there was no difference of CD86 and CD14 expression between the two groups(P>0.05).Conclusion:IL-34 played roles in the process of immature DC differentiation,but the effect was slightly weaker than that of GM-CSF.IL-34 did not effect the phenotype change of mature DC,but involved in the maintainence of immature DC.