Circulating follicular helper T cells presented distinctively different responses toward bacterial antigens in primary biliary cholangitis
Circulating follicular helper T cells presented distinctively different responses toward bacterial antigens in primary biliary cholangitis
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原发性胆汁性胆管炎中循环滤泡辅助 T 细胞对细菌抗原表现出明显不同的反应
DOI：
10.1016/j.intimp.2017.08.004
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发表时间：
2017-10
影响因子：
5.6
通讯作者：
Zheng-Yun Zhang
中科院分区：
文献类型：
--
作者：
Zun-Qiang Zhou;Da-Nian Tong;Jiao Guan;Mei-Fang Li;Qi-Ming Feng;Min-Jie Zhou;Zheng-Yun Zhang
原发性胆管炎(PBC)是一种病因不明的慢性进行性胆汁淤积性肝病。PBC的发生与细菌感染和异常免疫相关因素有关，如自身反应性抗线粒体抗体的存在和T细胞亚群平衡的改变。尤其是CD4+CXCR5+滤泡辅助性T细胞(TFH)在PBC患者中被高度激活，并与PBC的严重程度显著相关，但潜在原因尚不清楚。在这项研究中，我们发现循环中的CD_4+CXCR5+T细胞富含分泌干扰素γ的Th1亚型和分泌IL-17的Th17亚型，但不富含分泌IL-4的Th2亚型。我们进一步证明了包括Pam3CSK4、Poly(I：C)、脂多糖、咪喹莫特和CpG在内的一系列微生物基序能够显著刺激PBC患者循环γ+CXCR5+T细胞中的干扰素-CD8、IL-17和/或IL-21，尤其在单核细胞和B细胞存在的情况下。大肠埃希菌、芳香新冠杆菌和戈登分枝杆菌的完整菌体也能有效地刺激循环γ+CXCR5+T细胞产生干扰素-CXCR5和/或IL-21。但有趣的是，尽管全细胞可以有效地刺激健康对照组和PBC患者的循环中的CD4+CXCR5+T细胞，但细胞蛋白裂解物只有效地刺激PBC患者的循环中的CD4+CXCR5+T细胞，而不能刺激健康对照组的循环中的CD4+CXCR5+T细胞，这表明PBC患者的循环中的CD4+CXCR5+T细胞与健康人相比具有独特的抗原特异性。总之，这些数据表明，细菌抗原刺激是PBC患者Tfh细胞异常激活的潜在来源。
Primary biliary cholangitis (PBC) is a chronic and progressive cholestatic liver disease with unknown causes. The initiation of PBC is associated with bacterial infections and abnormal immune correlates, such as the presence of self-reactive anti-mitochondrial antibodies and shifted balance of T cell subsets. In particular, the CD4+CXCR5+follicular helper T (Tfh) cells are highly activated in PBC patients and are significantly associated with PBC severity, but the underlying reasons are unknown. In this study, we found that the circulating CD4+CXCR5+T cells were enriched with the interferon (IFN)-γ-secreting Th1-subtype and the interleukin (IL)-17-secreting Th17-subtype, but not the IL-4-secreting Th2 subtype. We further demonstrated that a host of microbial motifs, including Pam3CSK4, poly(I:C), LPS, imiquimod, and CpG, could significantly stimulate IFN-γ, IL-17, and/or IL-21 from circulating CD4+CXCR5+T cells in PBC patients, especially in the presence of monocytes and B cells. Whole bacterial cells ofEscherichia coli,Novosphingobium aromaticivorans, andMycobacterium gordonae, could also potently stimulate IFN-γ, IL-17, and/or IL-21 production from circulating CD4+CXCR5+T cells. But interestingly, while the whole cell could potently stimulate circulating CD4+CXCR5+T cells from both healthy controls and PBC patients, the cell protein lysate could only potently stimulate circulating CD4+CXCR5+T cells from PBC patients, but not those from healthy controls, suggesting that circulating CD4+CXCR5+T cells in PBC patients had distinctive antigen-specificity from those in healthy individuals. Together, these data demonstrated that bacterial antigen stimulation is a potential source of aberrant Tfh cell activation in PBC patients.
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影响因子：
30.5
作者：
通讯作者：
--
DOI：
--
发表时间：
--
期刊：
--
影响因子：
--
作者：
J. Talwalkar;K. Lindor;J. Talwalkar
通讯作者：
J. Talwalkar;K. Lindor;J. Talwalkar
DOI：
10.32388/cpmnhz
发表时间：
2020-02
期刊：
Definitions
影响因子：
--
作者：
H. A. Shah;H. Sheikh
通讯作者：
H. A. Shah;H. Sheikh
原发性胆汁性肝硬化
影响因子：
9.1
作者：
S. Reynoso‐Paz;R. Coppel;Vasuni Nakanuma;M. Gershwin
通讯作者：
M. Gershwin
原发性胆汁性胆管炎肠道微生物特征发生改变，UDCA 治疗后部分恢复
影响因子：
24.5
作者：
Tang, Ruqi;Wei, Yiran;Ma, Xiong
通讯作者：
Ma, Xiong