interleukin-7-aggravated joint inflammation and tissue destruction in collagen-induced arthritis is associated with t-cell and b-cell activationinterleukin-7-aggravated关节炎症和组织破坏胶原诱导关节炎与t细胞和b细胞活化相关.pdfVIP

Hartgring et al. Arthritis Research Therapy 2012, 14:R137 /content/14/3/R137 RESEARCH ARTICLE Open Access Interleukin-7-aggravated joint inflammation and tissue destruction in collagen-induced arthritis is associated with T-cell and B-cell activation 1* 2 1 1 1 Sarita AY Hartgring , Cynthia R Willis , Johannes WJ Bijlsma , Floris PJG Lafeber and Joel AG van Roon Abstract Introduction: We sought to investigate the capacity of interleukin (IL)-7 to enhance collagen-induced arthritis and to study by what mechanisms this is achieved. Methods: Mice received multiple injections with IL-7 or phosphate-buffered saline (PBS) as a control. Arthritis severity and incidence were determined by visual examination of the paws. Joint destruction was determined by assessing radiographs and immunohistochemistry of the ankle joints. Total cellularity and numbers of T-cell and B- cell subsets were assessed, as well as ex vivo production of interferon-g (IFN-g), IL-17, and IL-4. Proinflammatory mediators were measured in serum with multianalyte profiling. Results: IL-7 increased arthritis severity and radiology-assessed joint destruction. This was consistent with IL-7- + + + increased intensity of cell infiltrates, bone erosions, and cartilage damage. Splenic CD19 B cells and CD19 /GL7 germinal center B cells, as well as CD4 and CD8 numbers, were increased by IL-7. IL-7 expanded memory T cells, associated with increased percentages of IFN-g-, IL-4-, and IL-17-producing CD4+ T cells. On antigen restimulation of draining lymph node cells in vitro IL-7 tr