摘要：

ObjectiveTo study the effects of interleukin-7 receptor -chain (IL-7R) blockade on collagen-induced arthritis (CIA) and to investigate the effects on T cell numbers, T cell activity, and levels of proinflammatory mediators.MethodsWe studied the effect of anti–IL-7R antibody treatment on inflammation and joint destruction in CIA in mice. Numbers of thymocytes, splenocytes, T cell subsets, B cells, macrophages, and dendritic cells were assessed. Cytokines indicative of Th1, Th2, and Th17 activity and several proinflammatory mediators were assessed by multianalyte profiling in paw lysates. In addition, T cell–associated cytokines were measured in supernatants of lymph node cell cultures.ResultsAnti–IL-7R treatment significantly reduced clinical arthritis severity in association with reduced radiographic joint damage. Both thymic and splenic cellularity were reduced after treatment with anti–IL-7R. IL-7R blockade specifically reduced the total number of cells as well as numbers of naive, memory, CD4+, and CD8+ T cells from the spleen and significantly reduced T cell–associated cytokines (interferon-, IL-5, and IL-17). IL-7R blockade also decreased local levels of proinflammatory cytokines and factors associated with tissue destruction, including tumor necrosis factor , IL-1β, IL-6, matrix metalloproteinase 9, and RANKL. IL-7R blockade did not significantly affect B cells, macrophages, and dendritic cells. B cell activity, indicated by serum anticollagen IgG antibodies, was not significantly altered.ConclusionBlockade of IL-7R potently inhibited joint inflammation and destruction in association with specific reductions of T cell numbers, T cell–associated cytokines, and numerous mediators that induce inflammation and tissue destruction. This study demonstrates an important role of IL-7R–driven immunity in experimental arthritis and indicates the therapeutic potential of IL-7R blockade in human arthritic conditions.

展开