Sagami Shintaro, Ueno Yoshitaka, Tanaka Shinji, Fujita Akira, Niitsu Hiroaki, Hayashi Ryohei, Hyogo Hideyuki, Hinoi Takao, Kitadai Yasuhiko, Chayama Kazuaki
Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan.
Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan.
PLoS One. 2017 Jan 17;12(1):e0169681. doi: 10.1371/journal.pone.0169681. eCollection 2017.
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.
炎症性肠病（IBD）患者血清中胆碱及其衍生物的水平低于健康个体。然而，胆碱缺乏对结肠炎严重程度的影响尚未得到研究。在本研究中，我们调查了胆碱缺乏在葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎中的作用。与喂食对照（CTR）饮食的小鼠相比，蛋氨酸 - 胆碱缺乏（MCD）饮食降低了野生型B6小鼠结肠固有层、腹腔和肠系膜淋巴结中II型自然杀伤T（NKT）细胞的水平，并增加了肝脏中II型NKT细胞的水平。促进NKT细胞积累的趋化因子受体CXCR6的基因表达模式在结肠和肝脏之间因II型NKT细胞水平的变化而有所不同。为了研究胆碱缺乏条件下II型NKT细胞在结肠炎中的作用，我们评估了喂食MCD或CTR饮食的I型NKT细胞缺陷（Jα18-/-）或I型和II型NKT细胞缺陷（CD1d-/-）小鼠中DSS诱导的结肠炎的严重程度。MCD饮食导致Jα18-/-小鼠而非CD1d-/-小鼠的炎症减轻、干扰素（IFN）-γ和白细胞介素（IL）-4分泌减少以及产生IFN-γ和IL-4的NKT细胞数量减少。最后，将含有II型NKT细胞的淋巴细胞适应性转移加剧了喂食MCD饮食的Jα18-/-小鼠中DSS诱导的结肠炎。这些结果表明，胆碱缺乏导致促炎性II型NKT细胞丢失并减轻DSS诱导的结肠炎。因此，胆碱缺乏条件下DSS诱导的结肠炎中的炎症是由II型NKT细胞依赖性机制引起的，包括II型NKT细胞和促炎细胞因子水平降低。
