Increased intraarticular interleukin‐7 in rheumatoid arthritis patients stimulates cell contact–dependent activation of CD4+ T cells and macrophages

Intraarticular soluble interleukin‐17 receptor levels are increased in patients with rheumatoid arthritis and correlate with local mediators of inflammation: Comment on the article by Pickens et al

“…We read with interest the report by Pickens et al (1), in which they documented increased expression of interleukin-7 (IL-7) and IL-7 receptor (IL-7R␣) in the synovial tissue of patients with rheumatoid arthritis (RA), thereby supporting the findings of previous studies (2,3). In addition, they demonstrated increased coexpression of IL-7 and IL-7R␣ in the circulating monocytes, synovial fluid macrophages, endothelial cells, and fibroblasts of patients with RA compared with healthy control subjects.…”

“…First, although sIL-7R is produced from RA CD4ϩ T cells (3), we were unable to detect significantly increased levels of IL-7R in RA synovial tissue or peripheral blood T cells compared with normal cells. Second, although our group and others (3) showed that expression of IL-7R was significantly elevated…”

Proinflammatory mediator–induced reversal of CD4+,CD25+ regulatory T cell–mediated suppression in rheumatoid arthritis

“…In our experiments, we added 10 ng/ml of recombinant human IL-7, whereas the concentration of IL-7 in SF ranged from 15 to 186 pg/ml, and up to 500 pg/ml in previous studies (32). However, we believe this is a physiologically relevant concentration, since we previously showed that IL-7 influences effector T cell function (e.g., IFN␥ production) at very low dosages, starting at 10-100 pg/ml, with optimal responses at 10 ng/ml (34).…”

“…Recent work by us and by other investigators showed that IL-7 is produced by CD68ϩ monocytic cells in the rheumatoid synovium (32) as well as fibroblast-like synoviocytes (33). Furthermore, IL-7 induces TNF␣ production by RA monocytes, and IL-7 levels were shown to correlate with disease activity (32,34). IL-7 was recently suggested to reduce Treg-mediated suppression in JIA patients (35).…”

Cooperation between IL-7 Receptor and Integrin α2β1 (CD49b) Drives Th17-Mediated Bone Loss

“…IL-7 is an important cytokine involved in T cell survival and development, and as such has been shown to promote autoimmune diseases (9). In addition, in RA, IL-7 stimulates contactdependent activation of arthritic T cells and macrophages leading to TNF and metalloproteinase production (10,11). IL-7-aggravated joint inflammation in collagen-induced arthritis is also associated with expansion of Th1 and Th17 cells, although the mechanism by which it affects effector T cells is unclear (12).…”