Interleukin-7-aggravated joint inflammation and tissue destruction in collagen-induced arthritis is associated with T-cell and B-cell activation

• Published in: Arthritis research & therapy 2012-06, Vol.14 (3), p.R137-R137, Article R137
• Main Authors: Hartgring, Sarita A Y, Willis, Cynthia R, Bijlsma, Johannes W J, Lafeber, Floris P J G, van Roon, Joel A G
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Ankle Joint - immunology; Ankle Joint - pathology; Arthritis; Arthritis, Experimental - immunology; Arthritis, Experimental - pathology; B cells; B-Lymphocytes - immunology; Biological response modifiers; Collagen; Fibroblast growth factors; Flow Cytometry; Immunohistochemistry; Inflammation; Inflammation - immunology; Inflammation - pathology; Interferon; Interleukin-7; Interleukin-7 - immunology; Interleukins; Lymphocyte Activation - immunology; Male; Mice; Mice, Inbred DBA; Phosphates; Physiological aspects; T cells; T-Lymphocytes - immunology; Vascular endothelial growth factor
• ISSN: 1478-6354; 1478-6362; 1478-6354
• DOI: 10.1186/ar3870

We sought to investigate the capacity of interleukin (IL)-7 to enhance collagen-induced arthritis and to study by what mechanisms this is achieved. 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-γ (IFN-γ), IL-17, and IL-4. Proinflammatory mediators were measured in serum with multianalyte profiling. 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-γ-, IL-4-, and IL-17-producing CD4+ T cells. On antigen restimulation of draining lymph node cells in vitro IL-7 treatment was found to increase IFN-γ and IL-17 production, whereas IL-4 was reduced. IL-7 also increased concentrations of proinflammatory mediators, indicative of T-cell activation (sCD40L), vascular activation (VCAM-1, VEGF), tissue destruction (fibroblast growth factor-basic (FGF-b), LIF), and chemotaxis (MIP-1γ, MIP-3β, lymphotactin, MDC, and MCP-5). In arthritic mice, IL-7 causes expansion of T and B cells, associated with increased levels of proinflammatory mediators. IL-7 intensifies arthritis severity and joint destruction, accompanied by increased Th1 and Th17 activity. These data indicate that IL-7 could be an important mediator in arthritic conditions and that targeting IL-7 or its receptor represent novel therapeutic strategies.