Systemic lupus erythematosus (SLE) is the quintessential autoimmune disease, as it is characterized by hyperactivity of CD4+ T cells and subsequently drives lupus pathology. Follicular helper T (TFH) cells play an important role in B cell maturation and antibody production. However, which specific subset of cTFH cells drives B cell function and contributes to the development of anti-dsDNA antibodies and SLE pathogenesis remains unclear. Peripheral blood mononuclear cells from SLE patients with inactive (n = 11) and active (n = 21) were used to determine and detect frequencies and phenotypes of circulating TFH cells (cTFH), memory cTFH, and B cell subsets. The correlations among cTFH cell subsets and phenotypes, B cell subsets, anti-dsDNA autoantibodies, and clinical parameters were analyzed. In subjects with active SLE, cTFH1 and cTFH17 cells were significantly expanded and activated. These expanded cTFH cells expressed memory phenotypes; cTFH1 cells were predominantly central memory (CM) type, while cTFH17 cells were largely effector memory (EM) type. Phenotyping B cell subsets in these patients showed increased frequencies of aNAV and DN2 B cells. Clinically, ICOS+ cTFH1, ICOS+ cTFH17 cells, and SLEDAI-2k scores were found to be correlated. Analysis of cTFH-B cell relationship revealed positive correlations among ICOS+ cTFH1 cells, aNAV B cells, and anti-dsDNA antibodies. Activation of ICOS+ cTFH17 cells was significantly related to the expansion of aNAV and DN2 B cells. The presence of CM cells in cTFH1 and cTFH17 subsets was correlated with aNAV and DN2 B cell frequencies. SLE cTFH cells were found to be polarized toward cTFH1 and cTFH17 cells; activation of these cTFH subsets was significantly associated with disease activity score, aNAV, DN2 B cell expansion, and anti-dsDNA antibody level. Thus, the interactions among cTFH1, cTFH17, and B cells likely contribute to the development of autoantibodies and the pathogenesis in SLE.

中文翻译：

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系统性红斑狼疮患者中循环 TFH17 细胞的激活与激活的幼稚和双阴性 2 B 细胞扩增以及疾病活动相关


系统性红斑狼疮 (SLE) 是一种典型的自身免疫性疾病，其特点是 CD4+ T 细胞过度活跃，并随后导致狼疮病理。滤泡辅助 T (TFH) 细胞在 B 细胞成熟和抗体产生中发挥重要作用。然而，cTFH 细胞的哪个特定亚群驱动 B 细胞功能并有助于抗 dsDNA 抗体的发展和 SLE 发病机制仍不清楚。使用来自不活动 (n = 11) 和活动 (n = 21) 的 SLE 患者的外周血单核细胞来确定和检测循环 TFH 细胞 (cTFH)、记忆 cTFH 和 B 细胞亚群的频率和表型。分析 cTFH 细胞亚群和表型、B 细胞亚群、抗 dsDNA 自身抗体和临床参数之间的相关性。在患有活动性 SLE 的受试者中，cTFH1 和 cTFH17 细胞显着扩增和激活。这些扩增的 cTFH 细胞表达记忆表型； cTFH1细胞主要是中枢记忆（CM）型，而cTFH17细胞主要是效应记忆（EM）型。对这些患者的 B 细胞亚群进行表型分析显示 aNAV 和 DN2 B 细胞的频率增加。临床上发现ICOS+ cTFH1、ICOS+ cTFH17细胞和SLEDAI-2k评分之间存在相关性。 cTFH-B 细胞关系分析显示 ICOS+ cTFH1 细胞、aNAV B 细胞和抗 dsDNA 抗体之间呈正相关。 ICOS+ cTFH17 细胞的激活与 aNAV 和 DN2 B 细胞的扩增显着相关。 cTFH1 和 cTFH17 亚群中 CM 细胞的存在与 aNAV 和 DN2 B 细胞频率相关。 发现 SLE cTFH 细胞向 cTFH1 和 cTFH17 细胞极化；这些 cTFH 子集的激活与疾病活动评分、aNAV、DN2 B 细胞扩增和抗 dsDNA 抗体水平显着相关。因此，cTFH1、cTFH17 和 B 细胞之间的相互作用可能有助于自身抗体的产生和 SLE 的发病机制。