Long Yan, Xia Changsheng, Sun Yuanyuan, Ma Yinting, Xu Lijuan, Song Ying, Liu Chen
Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.
Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Centre, Beijing, China.
Immunol Lett. 2021 May;233:2-10. doi: 10.1016/j.imlet.2021.03.001. Epub 2021 Mar 3.
A recently identified population of T cells, phenotypically CD4PD-1CXCR5, has been firstly termed as peripheral helper T cells (Tph) and found to be pathogenic in autoimmune diseases. However, the potential role of Tph in ulcerative colitis (UC) remains unclear. We aim to investigate the changes of circulating Tph in UC patients and their potential significance in the pathogenesis of UC.
Totally 68 UC patients and 34 age- and sex-matched healthy controls were enrolled. Circulating Tph and B cell subsets were analyzed by flow cytometry. Expressions of inducible T-cell co-stimulator (ICOS) on Tph cells were analyzed. Serum IL-4, IL-10, IL-12 and IL-21 were detected using ELISA. Correlation analyses were conducted between Tph cells and disease severity, functional B cell subsets and serum cytokines.
Both the frequency and absolute number of Tph were significantly increased in active UC patients and ICOS levels in Tph cells were also elevated, compared with remission UC patients and healthy controls. Tph and ICOS expression were significantly positively correlated with Mayo score and serum CRP in active UC patients, and were significantly decreased when achieving remission after treatment. Tph levels were correlated with new memory B cells, plasmablasts, serum IL-4 and IL-21. Meanwhile, serum IL-10 showed negative correlation while IL-12 exhibited positive correlation with circulating Tph cells in UC patients.
Circulating Tph cells are elevated in active UC patients and are associated with the disease activity, which may contribute to the pathogenesis of UC.
最近鉴定出的一群T细胞,表型为CD4⁺PD-1⁺CXCR5⁺,最初被称为外周辅助性T细胞(Tph),并发现其在自身免疫性疾病中具有致病性。然而,Tph在溃疡性结肠炎(UC)中的潜在作用仍不清楚。我们旨在研究UC患者循环Tph的变化及其在UC发病机制中的潜在意义。
共纳入68例UC患者和34例年龄及性别匹配的健康对照。通过流式细胞术分析循环Tph和B细胞亚群。分析Tph细胞上诱导性T细胞共刺激分子(ICOS)的表达。采用酶联免疫吸附测定(ELISA)检测血清白细胞介素-4(IL-4)、白细胞介素-10(IL-10)、白细胞介素-12(IL-12)和白细胞介素-21(IL-21)。对Tph细胞与疾病严重程度、功能性B细胞亚群及血清细胞因子进行相关性分析。
与缓解期UC患者和健康对照相比,活动期UC患者Tph的频率和绝对数量均显著增加,Tph细胞中的ICOS水平也升高。活动期UC患者中,Tph和ICOS表达与梅奥评分及血清C反应蛋白(CRP)显著正相关,治疗后缓解时显著降低。Tph水平与新的记忆B细胞、浆母细胞、血清IL-4和IL-21相关。同时,UC患者血清IL-10与循环Tph细胞呈负相关,而IL-12与循环Tph细胞呈正相关。
活动期UC患者循环Tph细胞升高,且与疾病活动相关,这可能有助于UC的发病机制。