Hisamatsu Tadakazu, Erben Ulrike, Kühl Anja A
The Third Department of Internal Medicine, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Medical Department (Gastroenterology/Infectious Diseases/Rheumatology), Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Inflamm Intest Dis. 2016 Jul;1(2):52-62. doi: 10.1159/000445133. Epub 2016 Apr 9.
Chronic intestinal inflammation due to noninfectious causes represents a growing health issue all over the world. Celiac disease as well as inflammatory bowel diseases (IBD) like Crohn's disease and ulcerative and microscopic colitis involve uncontrolled T-cell activation and T-cell-mediated damage as common denominators. Therefore, diagnosis and treatment decisions clearly benefit from the knowledge of the intricacies of the systemic and the local T-cell activity.
Depending on the cytokine milieu, CD4 T cells can differentiate into proinflammatory T helper 1 (Th1), anti-inflammatory Th2, antimicrobial Th17, pleiotropic Th9, tissue-instructing Th22 cells, and in the regulatory compartment forkhead box protein 3 Treg, suppressive Tr1 or Th3 cells. Additionally, follicular Th cells provide B-cell help in antibody class switching; cytotoxic CD8 T cells target virus-infected or tumor cells. This review discusses our current knowledge on the contribution of defined T-cell subpopulations to establishing and maintaining chronic intestinal inflammation in either of the above entities. It also puts emphasis on the differences in the prevalence of these diseases between Eastern and Western countries.
In celiac disease, the driving role of T cells in the lamina propria and in the epithelium mainly specific for two defined antigens is well established. Differences in genetics and lifestyle between Western and Eastern countries were instrumental in understanding underlying mechanisms. In IBD, the vast amount of potential antigens and the corresponding antigen-specific T cells makes it unlikely to find universal triggers. Increased mucosal CD4 regulatory T cells in all four entities fail to control or abrogate local inflammatory processes. Thus, prevailing differences in the functional T-cell subtypes driving chronic intestinal inflammation in celiac disease and IBD at best allow some overlap in the treatment options for either disease.
非感染性原因导致的慢性肠道炎症在全球范围内已成为一个日益严重的健康问题。乳糜泻以及诸如克罗恩病、溃疡性结肠炎和显微镜下结肠炎等炎症性肠病（IBD）都存在共同特征，即T细胞不受控制的激活以及T细胞介导的损伤。因此，对于系统性和局部T细胞活动复杂性的了解显然有助于诊断和治疗决策。
根据细胞因子环境，CD4 T细胞可分化为促炎性辅助性T细胞1（Th1）、抗炎性Th2、抗微生物Th17、多效性Th9、组织指导型Th22细胞，以及调节性亚群中的叉头框蛋白3调节性T细胞（Treg）、抑制性Tr1或Th3细胞。此外，滤泡性Th细胞在抗体类别转换中为B细胞提供帮助；细胞毒性CD8 T细胞靶向病毒感染细胞或肿瘤细胞。本综述讨论了我们目前对于特定T细胞亚群在上述任何一种疾病中建立和维持慢性肠道炎症所起作用的认识。同时还强调了东西方国家这些疾病患病率的差异。
在乳糜泻中，固有层和上皮细胞中T细胞的驱动作用主要针对两种特定抗原，这一点已得到充分证实。东西方国家在遗传学和生活方式上的差异有助于理解其潜在机制。在IBD中，大量潜在抗原和相应的抗原特异性T细胞使得难以找到普遍的触发因素。在所有这四种疾病中，黏膜CD4调节性T细胞增加，但未能控制或消除局部炎症过程。因此，在乳糜泻和IBD中驱动慢性肠道炎症的功能性T细胞亚型的主要差异，最多只允许两种疾病在治疗选择上有一些重叠。
