Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
J Gastroenterol Hepatol. 2018 Jan;33(1):298-306. doi: 10.1111/jgh.13844.
Recent studies have demonstrated that B cells and follicular helper T (Tfh) cells, which are central regulators of humoral immune response, contribute to the development and progression of autoimmune diseases. Because Tfh cells can be divided into several subsets with distinct functional properties, this study aimed to examine the roles of different subsets of circulating Tfh cells in the immune pathogenesis of autoimmune hepatitis (AIH).
Thirty-five patients with AIH, 28 patients with primary biliary cholangitis, 22 patients with chronic hepatitis B (CHB), and 44 health controls (HC) were enrolled. The frequencies of different Tfh subsets in the blood and liver were examined by flow cytometry and immunohistochemical staining. The function of circulating Tfh subsets was examined after in vitro stimulation.
In newly diagnosed AIH patients, the frequency of circulating chemokine C-C receptor 7 programmed cell death-1 Tfh subset was significantly increased compared with that in CHB patients and HC, significantly correlated with clinical parameters, including serum IgG, prothrombin time and albumin levels, and significantly decreased after corticosteroid treatment. In the liver of AIH patients, the frequencies of activated Tfh subsets were significantly increased and positively correlated with those in the blood. Moreover, the ability to produce interleukin-21 and interleukin-17 from circulating Tfh cells was significantly increased in AIH patients compared with HC.
These results significantly extend our understanding of Tfh subsets in AIH and suggest a potential role of dysregulated chemokine C-C receptor 7 programmed cell death-1 Tfh subset in the pathogenesis and disease progression of AIH.
最近的研究表明，B 细胞和滤泡辅助 T（Tfh）细胞是体液免疫反应的中枢调节剂，它们参与了自身免疫性疾病的发生和发展。由于 Tfh 细胞可以分为具有不同功能特性的几个亚群，因此本研究旨在探讨循环 Tfh 细胞不同亚群在自身免疫性肝炎（AIH）免疫发病机制中的作用。
纳入 35 例 AIH 患者、28 例原发性胆汁性胆管炎患者、22 例慢性乙型肝炎（CHB）患者和 44 例健康对照者（HC）。采用流式细胞术和免疫组化染色检测血液和肝脏中不同 Tfh 亚群的频率。体外刺激后检测循环 Tfh 亚群的功能。
在新诊断的 AIH 患者中，循环趋化因子 C-C 受体 7 程序性细胞死亡蛋白-1 Tfh 亚群的频率明显高于 CHB 患者和 HC，与临床参数（包括血清 IgG、凝血酶原时间和白蛋白水平）显著相关，经皮质类固醇治疗后明显降低。在 AIH 患者的肝脏中，活化的 Tfh 亚群的频率明显增加，与血液中的频率呈正相关。此外，与 HC 相比，AIH 患者循环 Tfh 细胞产生白细胞介素-21 和白细胞介素-17 的能力明显增强。
这些结果显著扩展了我们对 AIH 中 Tfh 亚群的理解，并提示失调的趋化因子 C-C 受体 7 程序性细胞死亡蛋白-1 Tfh 亚群在 AIH 的发病机制和疾病进展中可能发挥作用。
