系统性红斑狼疮患者外周血滤泡辅助性 T 细胞（CD4CXCR5PD-1）和辅助性 T 细胞（CD4CXCR5PD-1）中 BAFFR 的表达。
BAFFR expression in circulating T follicular helper (CD4CXCR5PD-1) and T peripheral helper (CD4CXCR5PD-1) cells in systemic lupus erythematosus.
机构信息
Doctorado en Ciencias Biomédicas (DCB), Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, México.
División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara, México.
出版信息
Lupus. 2023 Aug;32(9):1093-1104. doi: 10.1177/09612033231189804. Epub 2023 Jul 17.
BACKGROUND
Circulating T follicular helper (cTfh) and T peripheral helper (Tph) subpopulations are shown to be higher in systemic lupus erythematosus (SLE) patients and have been involved in promoting extrafollicular B cell responses. However, a possible association with the B cell activating factor (BAFF), a cytokine mainly related to B cell responses and disease activity in SLE, has not been investigated. Therefore, this study aimed to evaluate the association of cTfh and Tph subpopulations with the BAFF system expression and clinical activity in SLE patients.
METHODS
This study included 43 SLE patients and 12 healthy subjects (HS). The identification of cTfh (CD4CXCR5PD-1), Tph (CD4CXCR5PD-1) cells, expression of membrane-bound BAFF (mBAFF), BAFFR, TACI, BCMA, and intracellular IL-21 was performed by flow cytometry. Serum levels of IL-21, CXCL13, and BAFF were analyzed using ELISA. The SLEDAI-2K score was used to evaluate disease activity in SLE patients.
RESULTS
Compared with HS, SLE patients showed a significantly increased percentage of cTfh and Tph cells, higher in patients with clearly active disease. SLE patients had markedly higher IL-21-producing cTfh and Tph cells than HS. Both subpopulations were positively correlated with the disease activity in SLE patients. Tph cells were negatively correlated with CD19CXCR5 B cells and positively correlated with CD19CXCR5 B cells. A low expression of mBAFF and their receptors TACI and BCMA was found on cTfh and Tph cells in SLE patients and HS. However, SLE patients with clearly active disease showed decreased expression of BAFFR on cTfh and Tph subpopulations than patients with mildly active/nonactive disease. Serum IL-21, CXCL13, and BAFF levels were higher in SLE patients than in HS. Levels of CXCL13 were correlated with disease activity. Non-significant correlations were observed among T cell subpopulations and IL-21, CXCL13, and BAFF levels.
CONCLUSIONS
This study emphasizes the importance of cTfh and Tph cells in SLE pathogenesis. Besides the importance of IL-21, our results suggest that BAFFR could play a role in cTfh and Tph subpopulations in the autoimmunity context.
背景
循环滤泡辅助性 T 细胞（cTfh）和外周滤泡辅助性 T 细胞（Tph）亚群在系统性红斑狼疮（SLE）患者中较高，并被认为参与了促进滤泡外 B 细胞反应。然而，BAFF（一种主要与 SLE 中的 B 细胞反应和疾病活动相关的细胞因子）与之可能存在关联尚未得到研究。因此，本研究旨在评估 cTfh 和 Tph 亚群与 SLE 患者的 BAFF 系统表达和临床活动的相关性。
方法
本研究纳入了 43 名 SLE 患者和 12 名健康对照者（HS）。通过流式细胞术鉴定 cTfh（CD4+CXCR5+PD-1+）、Tph（CD4+CXCR5+PD-1+）细胞，检测膜结合 BAFF（mBAFF）、BAFFR、TACI、BCMA 的表达以及细胞内 IL-21 的水平。采用 ELISA 法检测血清中 IL-21、CXCL13 和 BAFF 的水平。使用 SLEDAI-2K 评分评估 SLE 患者的疾病活动度。
结果
与 HS 相比，SLE 患者的 cTfh 和 Tph 细胞比例显著增加，且在疾病活动度高的患者中更高。SLE 患者的 IL-21 产生 cTfh 和 Tph 细胞明显高于 HS。两个亚群与 SLE 患者的疾病活动度均呈正相关。Tph 细胞与 CD19+CXCR5+B 细胞呈负相关，与 CD19+CXCR5+B 细胞呈正相关。SLE 患者和 HS 患者的 cTfh 和 Tph 细胞上 mBAFF 及其受体 TACI 和 BCMA 的表达均降低，但疾病活动度高的 SLE 患者的 cTfh 和 Tph 亚群上的 BAFFR 表达低于疾病活动度低/无的患者。SLE 患者的血清 IL-21、CXCL13 和 BAFF 水平高于 HS。CXCL13 水平与疾病活动度相关。T 细胞亚群与 IL-21、CXCL13 和 BAFF 水平之间无显著相关性。
结论
本研究强调了 cTfh 和 Tph 细胞在 SLE 发病机制中的重要性。除了 IL-21 的重要性外，我们的结果还表明，BAFFR 在自身免疫背景下可能在 cTfh 和 Tph 亚群中发挥作用。
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