Mucosal T cells expressing high levels of IL-7 receptor are potential targets for treatment of chronic colitis.
The IL-7/IL-7R-dependent signaling pathway plays a crucial role in regulating the immune response in intestinal mucosa. Here we demonstrate the pivotal role of this pathway in the development and treatment of chronic colitis. T cells expressing high levels of IL-7R were substantially infiltrated in the chronic inflamed mucosa of TCR alpha-chain knockout mice and IL-7 transgenic mice. Transfer of mucosal T cells expressing high levels of IL-7R, but not T cells expressing low levels of IL-7R, from these mice into recombinase-activating gene-2(-/-) mice induced chronic colitis. Selective elimination of T cells expressing high levels of IL-7R by administrating small amounts of toxin-conjugated anti-IL-7R Ab completely ameliorated established, ongoing colitis. These findings provide evidence that therapeutic approaches targeting mucosal T cells expressing high levels of IL-7R are effective in the treatment of chronic intestinal inflammation and may be feasible for use in the therapy of human inflammatory bowel disease.
Yamazaki
Motomi
M
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Yajima
Tomoharu
T
Tanabe
Masanobu
M
Fukui
Kazuto
K
Okada
Eriko
E
Okamoto
Ryuichi
R
Oshima
Shigeru
S
Nakamura
Tetsuya
T
Kanai
Takanori
T
Uehira
Masahiro
M
Takeuchi
Tsutomu
T
Ishikawa
Hiromichi
H
Hibi
Toshifumi
T
Watanabe
Mamoru
M
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002908:Chronic Disease; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D019673:Genes, T-Cell Receptor alpha; D018796:Immunoconjugates / Q000008:administration & dosage / Q000627:therapeutic use; D000922:Immunotoxins / Q000008:administration & dosage / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009699:N-Glycosyl Hydrolases / Q000008:administration & dosage / Q000627:therapeutic use; D010940:Plant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis* / Q000276:immunology; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation
D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D000922:Immunotoxins; D010940:Plant Proteins; D020395:Receptors, Interleukin-7; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins