Huang Enyu, Liu Ronghua, Lu Zhou, Liu Jiajing, Liu Xiaoming, Zhang Dan, Chu Yiwei
Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
Department of Dermatology, Shenzhen Hospital, Peking University, Shenzhen, Guangdong, 518036, China.
Biochem Biophys Res Commun. 2016 May 27;474(2):252-258. doi: 10.1016/j.bbrc.2016.04.024. Epub 2016 Apr 8.
Ulcerative colitis (UC) is a kind of inflammatory bowel diseases characterized by chronic inflammation and ulcer in colon, and UC patients have increased risk of getting colorectal cancer. NKT cells are cells that express both NK cell markers and semi-invariant CD1d-restricted TCRs, can regulate immune responses via secreting a variety of cytokines upon activation. In our research, we found that the NKT cell-deficient CD1d(-/-) mice had relieved colitis in the DSS-induced colitis model. Further investigations revealed that the colon of CD1d(-/-) mice expressed less neutrophil-attracting chemokine CXCL 1, 2 and 3, and had decreased neutrophil infiltration. Infiltrated neutrophils also produced less reactive oxygen species (ROS) and TNF-α, indicating they may cause less epithelial damage. In addition, colitis-associated colorectal cancer was also relieved in CD1d(-/-) mice. During colitis, NKT cells strongly expressed TNF-α, which could stimulate CXCL 1, 2, 3 expressions by the epithelium. In conclusion, NKT cells can regulate colitis via the NKT cell-epithelium-neutrophil axis. Targeting this mechanism may help to improve the therapy of UC and prevent colitis-associated colorectal cancer.
溃疡性结肠炎（UC）是一种以结肠慢性炎症和溃疡为特征的炎症性肠病，UC患者患结直肠癌的风险增加。自然杀伤T细胞（NKT细胞）是一类同时表达自然杀伤（NK）细胞标志物和半不变性CD1d限制性T细胞受体（TCR）的细胞，激活后可通过分泌多种细胞因子来调节免疫反应。在我们的研究中，我们发现NKT细胞缺陷的CD1d（-/-）小鼠在葡聚糖硫酸钠（DSS）诱导的结肠炎模型中结肠炎有所缓解。进一步研究发现，CD1d（-/-）小鼠的结肠表达较少的吸引中性粒细胞的趋化因子CXCL 1、2和3，中性粒细胞浸润减少。浸润的中性粒细胞产生的活性氧（ROS）和肿瘤坏死因子-α（TNF-α）也较少，表明它们可能对上皮造成的损伤较小。此外，CD1d（-/-）小鼠的结肠炎相关结直肠癌也有所缓解。在结肠炎期间，NKT细胞强烈表达TNF-α，TNF-α可刺激上皮细胞表达CXCL 1、2、3。总之，NKT细胞可通过NKT细胞-上皮细胞-中性粒细胞轴调节结肠炎。针对这一机制可能有助于改善UC的治疗并预防结肠炎相关结直肠癌。
