Department of Laboratory Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, China.
Department of Laboratory Medicine, Maoming People's Hospital, China.
Adv Clin Exp Med. 2024 Aug;33(8):889-899. doi: 10.17219/acem/189865.
T follicular helper (Tfh) cells drive humoral immunity by facilitating B cell responses, but the functional role of Tfh cells in the pathogenesis of idiopathic membranous nephropathy (IMN) remains unclear.
This study aimed to establish a rat experimental membranous nephropathy model, investigate the phenotypic characteristics of Tfh cells, and analyze a clinically significant correlation between Tfh cells.
Passive Heymann nephritis (PHN) rats were induced by immunizing Sprague Dawley rats with anti-Fx1A serum. The frequency of Tfh and B cell subsets was analyzed with flow cytometry (FC). The serum concentration of interleukin-21 (IL-21), the relative mRNA expression levels of IL-21 and B cell lymphoma 6 (Bcl-6) in spleen mononuclear cells (MNCs), and the kidney infiltration of CD4+ T cells and IL-21 were assessed. The potential correlations among these measures were analyzed.
In comparison with the control group, significantly increased percentages of Tfh cells, inducible T cell co-stimulator-positive (ICOS+) Tfh cells, and mRNA expression of Bcl-6 were detected in the spleen of PHN rats. Elevated IL-21 expression was detected in the serum and kidneys. Remarkably, the percentage of splenic ICOS+ Tfh cells was positively correlated with 24 h urine protein concentrations (r = 0.676, p = 0.011) in PHN rats.
These data indicate that ICOS+ Tfh cells contribute to development of IMN, and they might be potential therapeutic targets for IMN.
滤泡辅助性 T 细胞（Tfh）通过促进 B 细胞反应来驱动体液免疫，但 Tfh 细胞在特发性膜性肾病（IMN）发病机制中的功能作用尚不清楚。
本研究旨在建立大鼠实验性膜性肾病模型，研究 Tfh 细胞的表型特征，并分析 Tfh 细胞与临床的显著相关性。
通过用抗 Fx1A 血清免疫 Sprague Dawley 大鼠诱导被动性 Heymann 肾炎（PHN）大鼠。采用流式细胞术（FC）分析 Tfh 和 B 细胞亚群的频率。检测血清白细胞介素 21（IL-21）浓度、脾单个核细胞（MNC）中 IL-21 和 B 细胞淋巴瘤 6（Bcl-6）的相对 mRNA 表达水平，以及 CD4+T 细胞和 IL-21 在肾脏中的浸润。分析这些措施之间的潜在相关性。
与对照组相比，PHN 大鼠脾脏中 Tfh 细胞、诱导型 T 细胞共刺激因子阳性（ICOS+）Tfh 细胞和 Bcl-6 的 mRNA 表达显著增加。血清和肾脏中 IL-21 表达升高。值得注意的是，PHN 大鼠脾脏中 ICOS+Tfh 细胞的百分比与 24 小时尿蛋白浓度呈正相关（r = 0.676，p = 0.011）。
这些数据表明 ICOS+Tfh 细胞有助于 IMN 的发展，它们可能是 IMN 的潜在治疗靶点。
