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.
Highlights
Inflammatory bowel diseases (IBDs) such as Crohn’s disease (CD) and ulcerative colitis (UC) result from uncontrolled intestinal immune responses toward commensal microflora and dietary antigens [1], as well as uncontrolled genetic abnormalities [2]
We examined the role of choline in dextran sulfate sodium (DSS)-induced colitis in mice to determine whether the immunopathogenesis of colitis is affected by choline deficiency
The results presented here highlight a new role for choline, demonstrating that choline deficiency causes colonic type II natural killer T (NKT) cell loss and alleviates DSS-induced colitis (S3A and S3B Fig)
Summary
Inflammatory bowel diseases (IBDs) such as Crohn’s disease (CD) and ulcerative colitis (UC) result from uncontrolled intestinal immune responses toward commensal microflora and dietary antigens [1], as well as uncontrolled genetic abnormalities [2]. CD and UC patients have lower levels of choline and its derivatives than healthy individuals. Choline and glycerophosphorylcholine are significantly lower in the mucosa of UC and CD patients experiencing active phases than in healthy controls and UC and CD patients in remission [6]. PC, and glycerophosphorylcholine are caused by an increased use of choline owing to inflammation in CD and UC patients [8]. Changes in trimethylamine (TMA) caused by gut microflora induce perturbations in choline metabolism, which contributes to nonalcoholic steatohepatitis (NASH) by reducing choline bioavailability [9, 10]. Very low-density lipoproteins (VLDLs) are downregulated in UC remission patients compared with active patients [7], as PC biosynthesis is required for the formation of VLDLs in the liver [11]. Deficiencies in choline and PC predispose patients to NAFLD via VLDL deficiency [12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
