title: Choline Deficiency Causes Colonic Type II Natural Killer T (NKT) Cell Loss and Alleviates Murine Colitis under Type I NKT Cell Deficiency.
abstract: Serum levels of choline and its derivatives are lower in patients with inflammatory bowel disease (IBD) than in healthy individuals. However, the effect of choline deficiency on the severity of colitis has not been investigated. In the present study, we investigated the role of choline deficiency in dextran sulfate sodium (DSS)-induced colitis in mice. Methionine-choline-deficient (MCD) diet lowered the levels of type II natural killer T (NKT) cells in the colonic lamina propria, peritoneal cavity, and mesenteric lymph nodes, and increased the levels of type II NKT cells in the livers of wild-type B6 mice compared with that in mice fed a control (CTR) diet. The gene expression pattern of the chemokine receptor CXCR6, which promotes NKT cell accumulation, varied between colon and liver in a manner dependent on the changes in the type II NKT cell levels. To examine the role of type II NKT cells in colitis under choline-deficient conditions, we assessed the severity of DSS-induced colitis in type I NKT cell-deficient (Jα18-/-) or type I and type II NKT cell-deficient (CD1d-/-) mice fed the MCD or CTR diets. The MCD diet led to amelioration of inflammation, decreases in interferon (IFN)-γ and interleukin (IL)-4 secretion, and a decrease in the number of IFN-γ and IL-4-producing NKT cells in Jα18-/- mice but not in CD1d-/- mice. Finally, adaptive transfer of lymphocytes with type II NKT cells exacerbated DSS-induced colitis in Jα18-/- mice with MCD diet. These results suggest that choline deficiency causes proinflammatory type II NKT cell loss and alleviates DSS-induced colitis. Thus, inflammation in DSS-induced colitis under choline deficiency is caused by type II NKT cell-dependent mechanisms, including decreased type II NKT cell and proinflammatory cytokine levels.
authors.affiliation: Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Sagami
authors.affiliation: Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ueno
authors.affiliation: Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Fujita
authors.affiliation: Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Niitsu
authors.affiliation: Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Hayashi
authors.affiliation: Department of Gastroenterology, Hiroshima General Hospital, Hiroshima, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hyogo
authors.affiliation: Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.|Department of Surgery, Institute for Clinical Research, National Hospital Organization Kure Medical Center and Chu-goku Cancer Center, Hiroshima, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Hinoi
authors.affiliation: Department of Life Sciences, Prefectural University of Hiroshima, Hiroshima, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kitadai
authors.affiliation: Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
mesh_terms: D000818:Animals; D002796:Choline Deficiency / Q000150:complications*; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control*; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D007371:Interferon-gamma; D016264:Dextran Sulfate