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Background 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. Methods We examined the contribution of IL-7R on inflammation and disease development in two models of experimental colitis: Helicobacter bilis ( Hb )-induced colitis in immune-sufficient Mdr1a −/− mice and in T- and B-cell-deficient Rag2 −/− 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. Results Treatment of mice with an anti-IL-7R antibody was effective in reducing colitis in Hb -infected Mdr1a −/− mice by reducing T-cell numbers as well as T-cell function. Down regulation of the innate immune response was also detected in Hb -infected Mdr1a −/− mice treated with an anti-IL-7R antibody. In Rag2 −/− mice where colitis was triggered by Hb -infection, treatment with an anti-IL-7R antibody controlled innate inflammatory responses by reducing macrophage and dendritic cell numbers and their activity. Conclusions Results from our studies showed that inhibition of IL-7R successfully ameliorated inflammation and disease development in Hb -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.

The Einstein Telescope (ET), the European project for a third-generation gravitational-wave detector, has a reference configuration based on a triangular shape consisting of three nested detectors with 10 km arms, where in each arm there is a `xylophone' configuration made of an interferometer tuned toward high frequencies, and an interferometer tuned toward low frequencies and working at cryogenic temperature. Here, we examine the scientific perspectives under possible variations of this reference design. We perform a detailed evaluation of the science case for a single triangular geometry observatory, and we compare it with the results obtained for a network of two L-shaped detectors (either parallel or misaligned) located in Europe, considering different choices of arm-length for both the triangle and the 2L geometries. We also study how the science output changes in the absence of the low-frequency instrument, both for the triangle and the 2L configurations. We examine a broad class of simple `metrics' that quantify the science output, related to compact binary coalescences, multi-messenger astronomy and stochastic backgrounds, and we then examine the impact of different detector designs on a more specific set of scientific objectives.