Systemic, but not intestinal, IL-7 is essential for the persistence of chronic colitis.
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.
Tomita
Takayuki
T
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Kanai
Takanori
T
Nemoto
Yasuhiro
Y
Totsuka
Teruji
T
Okamoto
Ryuichi
R
Tsuchiya
Kiichiro
K
Sakamoto
Naoya
N
Watanabe
Mamoru
M
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
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D015851:Interleukin-7; C499308:Rag2 protein, mouse; C064658:RAG-1 protein