<p>Abstract</p> <p>Background</p> <p>Interleukin-7 (IL-7) acts primarily on T cells to promote their differentiation, survival, and homeostasis. Under disease conditions, IL-7 mediates inflammation through several mechanisms and cell types. In humans, IL-7 and its receptor (IL-7R) are increased in diseases characterized by inflammation such as atherosclerosis, rheumatoid arthritis, psoriasis, multiple sclerosis, and inflammatory bowel disease. In mice, overexpression of IL-7 results in chronic colitis, and T-cell adoptive transfer studies suggest that memory T cells expressing high amounts of IL-7R drive colitis and are maintained and expanded with IL-7. The studies presented here were undertaken to better understand the contribution of IL-7R in inflammatory bowel disease in which colitis was induced with a bacterial trigger rather than with adoptive transfer.</p> <p>Methods</p> <p>We examined the contribution of IL-7R on inflammation and disease development in two models of experimental colitis: <it>Helicobacter bilis</it> (<it>Hb</it>)-induced colitis in immune-sufficient <it>Mdr1a</it><sup>−/−</sup> mice and in T- and B-cell-deficient <it>Rag2</it><sup>−/−</sup> mice. We used pharmacological blockade of IL-7R to understand the mechanisms involved in IL-7R-mediated inflammatory bowel disease by analyzing immune cell profiles, circulating and colon proteins, and colon gene expression.</p> <p>Results</p> <p>Treatment of mice with an anti-IL-7R antibody was effective in reducing colitis in <it>Hb</it>-infected <it>Mdr1a</it><sup>−/−</sup> mice by reducing T-cell numbers as well as T-cell function. Down regulation of the innate immune response was also detected in <it>Hb</it>-infected <it>Mdr1a</it><sup>−/−</sup> mice treated with an anti-IL-7R antibody. In <it>Rag2</it><sup>−/−</sup> mice where colitis was triggered by <it>Hb</it>-infection, treatment with an anti-IL-7R antibody controlled innate inflammatory responses by reducing macrophage and dendritic cell numbers and their activity.</p> <p>Conclusions</p> <p>Results from our studies showed that inhibition of IL-7R successfully ameliorated inflammation and disease development in <it>Hb</it>-infected mice by controlling the expansion of multiple leukocyte populations, as well as the activity of these immune cells. Our findings demonstrate an important function of IL-7R-driven immunity in experimental colitis and indicate that the therapeutic efficacy of IL-7R blockade involves affecting both adaptive and innate immunity.</p
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