Impaired granzyme B-producing regulatory B cells in systemic lupus erythematosus
Impaired granzyme B-producing regulatory B cells in systemic lupus erythematosus
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系统性红斑狼疮中产生颗粒酶 B 的调节性 B 细胞受损
DOI：
10.1016/j.molimm.2021.09.012
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发表时间：
2021-11-05
影响因子：
3.6
通讯作者：
Su, Yin
中科院分区：
文献类型：
--
作者：
Bai, Mingxin;Xu, Liling;Su, Yin
产生颗粒酶 B (GrB) 的 B 细胞被认为是一种调节性 B 细胞 (Breg)，并已被揭示与自身免疫性疾病的发病机制有关。然而，它们在 SLE 中的作用仍然难以捉摸。本研究通过流式细胞术评估健康对照组（HC）和系统性红斑狼疮（SLE）外周血中产生GrB的Bregs频率，并分析其与SLE患者临床和免疫学特征的相关性。通过RT-qPCR分析和ELISpot进一步检测HC和SLE B细胞中GrB的表达。通过采用 GrB 阻断的体外 CD4(+) 效应 T 细胞-B 细胞共培养测定，进一步研究了 HC 和 SLE 患者中产生 GrB 的 Breg 的功能。我们发现 SLE 患者中产生 GrB 的 Breg 显着减少，并且与临床和免疫学特征相关。此外，这些细胞在 SLE 情况下功能受损。在健康个体中观察到的产生 GrB 的 Breg 细胞与 CD4(+) T 细胞之间的负相关性在 SLE 患者中消失了。体外细胞共培养试验进一步表明，SLE 患者产生 GrB 的 Bregs 未能抑制 Th1、Th2 和 Th17 细胞炎症反应，部分原因是下调 TCR zeta 和诱导 T 细胞凋亡的能力减弱。总而言之，这些结果揭示了 SLE 中产生 GrB 的 Breg 受到干扰，这可能有助于疾病的发生和进展。
Granzyme B (GrB)-producing B cells are proposed to be a kind of regulatory B cells (Bregs) and have been revealed to be implicated in the pathogenesis of autoimmune diseases. Nevertheless, their role in SLE remains elusive. In this study, the frequencies of GrB-producing Bregs in peripheral blood of heathy control (HC) and systemic lupus erythematosus (SLE) were evaluated by flow cytometry, and their correlation with SLE patient clinical and immunological features were analyzed. The expression of GrB in HC and SLE B cells were also further detected by RT-qPCR analysis and ELISpot. The function of GrB-producing Bregs in HC and SLE patients was further investigated by in vitro CD4(+) effector T cells-B cells co-culture assays with GrB blockade. We found that GrB-producing Bregs were significantly decreased in SLE patients and correlated with the clinical and immunological features. Moreover, these cells were functionally impaired under SLE circumstance. The negative correlation between GrB-producing Bregs and CD4(+) T cells observed in healthy individuals disappeared in SLE patients. In vitro cell co-culture assay further showed that GrB-producing Bregs from SLE patients failed to suppress the Th1, Th2 and Th17 cell inflammatory responses, partially due to the dampened capacity of down-regulating TCR zeta and inducing T cell apoptosis. Taken together, these results revealed the disturbance of GrB-producing Bregs in SLE that might contribute to the disease initiation and progression.