Interleukin-7 receptor blockade suppresses adaptive and innate inflammatory responses in experimental colitis

• Published in: Journal of inflammation (London, England) England), 2012-10, Vol.9 (1), p.39-39
• Main Authors: Willis, Cynthia R, Seamons, Audrey, Maxwell, Joe, Treuting, Piper M, Nelson, Laurel, Chen, Guang, Phelps, Susan, Smith, Carole L, Brabb, Thea, Iritani, Brian M, Maggio-Price, Lillian
• Format: Article
• Language: English
• Subjects: Adoptive transfer; Analysis; Animal models; Antibodies; Arteriosclerosis; Arthritis; Atherosclerosis; Biotechnology industry; Cell survival; Colitis; Colon; Dendritic cells; Development and progression; Differentiation; Gastrointestinal diseases; Gene expression; Helicobacter bilis; Homeostasis; IL-7R; Immune system; Immunity; Immunological memory; Inflammation; Inflammatory bowel disease; Inflammatory bowel diseases; Interleukin 7; Interleukins; Leukocytes; Lymphocytes T; Macrophages; Mdr1a−/− mice; Memory cells; Multidrug resistance; Multiple sclerosis; Proteins; Psoriasis; RAG2 protein; Rag2−/− mice; Rheumatoid arthritis; Rheumatoid factor; Rodents; Studies; T cells
• ISSN: 1476-9255; 1476-9255
• DOI: 10.1186/1476-9255-9-39

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. 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. 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. 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.