School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
1st Department of Nephrology, Hippokration General Hospital, 54642 Thessaloniki, Greece.
Int J Mol Sci. 2024 Oct 10;25(20):10905. doi: 10.3390/ijms252010905.
Systemic lupus erythematosus (SLE) is a complex autoimmune disease, characterized by considerable changes in peripheral lymphocyte structure and function, that plays a critical role in commencing and reviving the inflammatory and immune signaling pathways. In healthy individuals, B lymphocytes have a major role in guiding and directing defense mechanisms against pathogens. Certain changes in B lymphocyte phenotype, including alterations in surface and endosomal receptors, occur in the presence of SLE and lead to dysregulation of peripheral B lymphocyte subpopulations. Functional changes are characterized by loss of self-tolerance, intra- and extrafollicular activation, and increased cytokine and autoantibody production. T lymphocytes seem to have a supporting, rather than a leading, role in the disease pathogenesis. Substantial aberrations in peripheral T lymphocyte subsets are evident, and include a reduction of cytotoxic, regulatory, and advanced differentiated subtypes, together with an increase of activated and autoreactive forms and abnormalities in follicular T cells. Up-regulated subpopulations, such as central and effector memory T cells, produce pre-inflammatory cytokines, activate B lymphocytes, and stimulate cell signaling pathways. This review explores the pivotal roles of B and T lymphocytes in the pathogenesis of SLE and Lupus Nephritis, emphasizing the multifaceted mechanisms and interactions and their phenotypic and functional dysregulations.
系统性红斑狼疮(SLE)是一种复杂的自身免疫性疾病,其特征是外周淋巴细胞结构和功能发生显著变化,在启动和恢复炎症和免疫信号通路方面发挥着关键作用。在健康个体中,B 淋巴细胞在引导和指导针对病原体的防御机制方面发挥着主要作用。在 SLE 存在的情况下,B 淋巴细胞表型发生某些变化,包括表面和内体受体的改变,导致外周 B 淋巴细胞亚群失调。功能变化的特征是自身耐受性丧失、滤泡内和滤泡外激活以及细胞因子和自身抗体产生增加。T 淋巴细胞在疾病发病机制中似乎起辅助作用,而不是主导作用。在外周 T 淋巴细胞亚群中存在明显的显著异常,包括细胞毒性、调节和高级分化亚型减少,同时激活和自身反应形式增加以及滤泡 T 细胞异常。上调的亚群,如中央和效应记忆 T 细胞,产生前炎症细胞因子,激活 B 淋巴细胞,并刺激细胞信号通路。本文探讨了 B 和 T 淋巴细胞在 SLE 和狼疮性肾炎发病机制中的关键作用,强调了多方面的机制和相互作用及其表型和功能失调。