Department of Medicine II, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Germany.
J Crohns Colitis. 2019 Dec 10;13(12):1546-1557. doi: 10.1093/ecco-jcc/jjz090.
Dysregulated T cell responses contribute to the pathogenesis of inflammatory bowel disease [IBD]. Because vitamin D [vitD] deficiency is a risk factor for adverse disease outcomes, we aimed to characterize the impact of vitD on intestinal and peripheral T cell profiles.
T cells were isolated from peripheral blood and intestinal biopsies of IBD patients, incubated with vitD and characterized by flow cytometry. To translate these in vitro findings to the clinic, serum vitD concentrations and clinical outcomes were correlated with T cell phenotype and function in a prospective patient cohort.
Incubation of peripheral and intestinal T cells with 1,25(OH)2-vitD resulted in strongly reduced frequencies of pro-inflammatory CD4+ and CD8+ T cells producing interferon γ [IFNγ], interleukin-17 [IL-17], IL-22, IL-9 and tumour necrosis factor [TNF]. Univariable analysis of 200 IBD patients revealed associations of vitD deficiency with non-compliant vitD intake, season of the year and anaemia in Crohn's disease [CD] as well as disease activity in ulcerative colitis [UC]. Ex vivo immunophenotyping revealed that CD4+ and CD8+ T cell subsets were not substantially altered in vitD-deficient vs vitD-sufficient patients while regulatory T cell frequencies were reduced in UC and non-smoking CD patients with vitD deficiency. However, normalization of serum vitD concentrations in previously deficient CD patients resulted in significantly reduced frequencies of CD4+ T cells producing IFNγ, IL-17 and IL-22.
vitD exerts profound anti-inflammatory effects on peripheral and intestinal CD4+ and CD8+ T cells of IBD patients in vitro and inhibits TH1 and TH17 cytokine production in CD patients in vivo.
T 细胞功能紊乱与炎症性肠病（IBD）的发病机制有关。由于维生素 D（vitD）缺乏是疾病不良结局的危险因素，我们旨在研究维生素 D 对肠道和外周 T 细胞谱的影响。
从 IBD 患者的外周血和肠道活检中分离 T 细胞，与 vitD 孵育并用流式细胞术进行表型鉴定。为了将这些体外研究结果转化到临床，我们在一个前瞻性的患者队列中，将血清 vitD 浓度和临床结局与 T 细胞表型和功能相关联。
外周和肠道 T 细胞与 1,25（OH）2-vitD 孵育后，产生干扰素 γ（IFNγ）、白细胞介素-17（IL-17）、IL-22、IL-9 和肿瘤坏死因子（TNF）的促炎 CD4+和 CD8+T 细胞的频率明显降低。对 200 例 IBD 患者的单变量分析显示，vitD 缺乏与克罗恩病（CD）中不遵医嘱摄入 vitD、一年中的季节和贫血以及溃疡性结肠炎（UC）中的疾病活动有关。体外免疫表型分析显示，vitD 缺乏与 vitD 充足患者相比，CD4+和 CD8+T 细胞亚群并未发生实质性改变，而 UC 和非吸烟 CD 患者的调节性 T 细胞频率在 vitD 缺乏时降低。然而，在先前缺乏 vitD 的 CD 患者中，血清 vitD 浓度的正常化显著降低了产生 IFNγ、IL-17 和 IL-22 的 CD4+T 细胞的频率。
vitD 对 IBD 患者的外周和肠道 CD4+和 CD8+T 细胞具有显著的抗炎作用，并在体内抑制 CD 患者的 TH1 和 TH17 细胞因子产生。
