title: Systemic, but not intestinal, IL-7 is essential for the persistence of chronic colitis.
abstract: We previously demonstrated that IL-7 is produced by intestinal goblet cells and is essential for the persistence of colitis. It is well known, however, that goblet cells are decreased or depleted in the chronically inflamed mucosa of animal colitis models or human inflammatory bowel diseases. Thus, in this study, we assess whether intestinal IL-7 is surely required for the persistence of colitis using a RAG-1/2-/- colitis model induced by the adoptive transfer of CD4+CD45RBhigh T cells in combination with parabiosis system. Surprisingly, both IL-7-/-xRAG-1-/- and IL-7+/+xRAG-1-/- host mice developed colitis 4 wk after parabiosis to a similar extent of colitic IL-7+/+xRAG-1-/- donor mice that were previously transferred with CD4+CD45RBhigh T cells. Of note, although the number of CD4+ T cells recovered from the spleen or the bone marrow of IL-7-/-xRAG-1-/- host mice was significantly decreased compared with that of IL-7+/+xRAG-1-/- host mice, an equivalent number of CD4+ T cells was recovered from the lamina propria of both mice, indicating that the expansion of CD4+ T cells in the spleen or in the bone marrow is dependent on IL-7, but not in the lamina propria. Development of colitis was never observed in parabionts between IL-7+/+xRAG-1-/- host and noncolitic IL-7-/-xRAG-1-/- donor mice that were transferred with CD4+CD45RBhigh T cells. Collectively, systemic, but not intestinal, IL-7 is essential for the persistence of colitis, suggesting that therapeutic approaches targeting the systemic IL-7/IL-7R signaling pathway may be feasible in the treatment of inflammatory bowel diseases.
authors: Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Takayuki
authors: T
authors: Tomita
authors: Takanori
authors: T
authors: Kanai
authors: Yasuhiro
authors: Y
authors: Nemoto
authors: Teruji
authors: T
authors: Totsuka
authors: Ryuichi
authors: R
authors: Okamoto
authors: Kiichiro
authors: K
authors: Tsuchiya
authors: Naoya
authors: N
authors: Sakamoto
authors: Mamoru
authors: M
authors: Watanabe
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D003092:Colitis / Q000276:immunology* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D018398:Homeodomain Proteins / Q000235:genetics; D015851:Interleukin-7 / Q000235:genetics / Q000502:physiology*; D007422:Intestines / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D009092:Mucous Membrane / Q000276:immunology; D010227:Parabiosis
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D015851:Interleukin-7; C499308:Rag2 protein, mouse; C064658:RAG-1 protein