Department of Rheumatology and Clinical Immunology, Faculty of Medicine, University of Thessaly, Larissa, Greece.
Department of Neurology, Faculty of Medicine, University of Thessaly, Larissa, Greece.
Front Immunol. 2024 May 21;15:1325356. doi: 10.3389/fimmu.2024.1325356. eCollection 2024.
Circulating T follicular helper (cTfh) cells and circulating T peripheral helper (cTph) cells (which share common characteristics with the cTfh population) are implicated in the pathogenesis of immune-mediated and autoimmune diseases such as psoriasis (Ps). Their close interplay with the interleukin 17 (IL-17) axis and the ex vivo effect of IL-17-targeting biologic agents used to treat Ps on them are elusive. This study aimed to investigate the effect of biologics targeting IL-17 on cTfh and cTph cell subpopulations isolated from the blood of patients with Ps.
Peripheral blood mononuclear cells (PBMCs) were isolated from patients with Ps at treatment initiation and three months later. Samples were also collected from controls. Cells were stained using monoclonal antibodies. Flow cytometry assessed the fraction of cTfh (CD3CD4CXCR5) and cTph (CD3CD4CXCR5PD-1) cells..
Flow cytometric analysis showed increased fractions of activated cTfh subsets including ICOS and ICOSPD-1 expressing cells, in patients compared to controls. Biologic blocking of IL-17A diminished the cTfh population. Furthermore, ICOS and ICOSPD-1 sub-populations were also inhibited. Finally, the cTph cell fraction significantly decreased after three months of successful treatment with biologics.
Early anti-IL-17-mediated clinical remission in Ps is associated with decreased cTfh and cTph cell subpopulations.
循环滤泡辅助性 T 细胞(cTfh)和循环外周辅助性 T 细胞(cTph)(与 cTfh 群体具有共同特征)与免疫介导和自身免疫性疾病(如银屑病(Ps))的发病机制有关。它们与白细胞介素 17(IL-17)轴的密切相互作用以及用于治疗 Ps 的 IL-17 靶向生物制剂对它们的体外作用仍不清楚。本研究旨在研究针对 IL-17 的生物制剂对从 Ps 患者血液中分离的 cTfh 和 cTph 细胞亚群的影响。
在治疗开始时和三个月后从 Ps 患者和对照者中分离外周血单核细胞(PBMC)。使用单克隆抗体对细胞进行染色。流式细胞术评估 cTfh(CD3CD4CXCR5)和 cTph(CD3CD4CXCR5PD-1)细胞的亚群分数。
流式细胞术分析显示,与对照者相比,患者中激活的 cTfh 亚群包括 ICOS 和 ICOSPD-1 表达细胞的比例增加。IL-17A 的生物阻断减少了 cTfh 群体。此外,ICOS 和 ICOSPD-1 亚群也受到抑制。最后,生物制剂治疗三个月后,cTph 细胞亚群显著减少。
Ps 中早期抗 IL-17 介导的临床缓解与 cTfh 和 cTph 细胞亚群减少有关。