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352 From animal models to human – a phenotypic and functional study of pdcs
  1. Z Zhou1,
  2. M Jianyang1,
  3. Q Rong2 and
  4. S Nan1
  1. 1Renji Hospital- School of Medicine- Shanghai Jiaotong University, Shanghai Institute of Rheumatology, Shanghai, China
  2. 2Shanghai Institutes for Biological Sciences SIBS and Shanghai Jiao Tong University School of Medicine SJTUSM- Chinese Academy of Sciences CAS, Institute of Health Sciences, Shanghai, China

Abstract

Background and aims To study the role of plasmacytoid dendritic cells(pDCs) in the pathogenesis of systemic lupus erythematosus(SLE)

Methods Totally 9 mouse strains were studied including NZB, NZW, NZBW F1, MRL/lpr, MRL/Mp, BXSB/Mp, BXSB.B6.Yaa, B6.SLE1.2.3 and C57BL/6. Spleen, thymus, bone marrow and lymph node pDCs were collected from mice in different disease stages by using Nycodenz enrichment and sorting systems. Human pDCs from healthy donor and SLE patients were isolated by using BDCA4 beads selection. Mouse pDCs were stimulated with ODN2216 and Poly U for Tlr9 and Tlr7 respectively. Human pDCs were stimulated with ODN2216 and R837 for Tlr9 and Tlr7 respectively. After 18 hour for human and 36 hour for mouse, supernatant was collected for ELISA test. IFNa, TNFa, and IL6 were tested.

Results Bone marrow pDC could produce much higher IFNa than pDCs from spleen, thymus and lymph node in all tested strains. pDCs from NZB, NZBW F1 could produce higher IFNa than those from other strains. Spleen pDCs from MRL/lpr and MRL/Mp mice could produce higher levels of IFNa via Tlr7 than Tlr9 stimulation. All lupus-prone mice except BXSB/Mp and B6.SLE1.2.3 strains have higher total pDCs numbers. Cytokine-producing ability of pDCs were reduced in mice with advanced disease stage. pDCs from SLE patients could produce higher IFNa than those from a healthy donor.

Conclusions Phenotype and function of pDCs were largely dependent on their genetic background. Activation and function alterations of pDCs were observed in a lupus model. Hyperactive of pDC from SLE patients may contribute to lupus pathogenesis.

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