关键词: PBMCs anti-IL-17 brodalumab cTfh cTph psoriasis psoriatic disease secukinumab

Mesh : Humans Psoriasis / immunology drug therapy Male Female Interleukin-17 / metabolism antagonists & inhibitors Adult Middle Aged Biological Products / therapeutic use pharmacology T Follicular Helper Cells / immunology T-Lymphocytes, Helper-Inducer / immunology metabolism drug effects T-Lymphocyte Subsets / immunology metabolism drug effects

来  源:   DOI:10.3389/fimmu.2024.1325356   PDF(Pubmed)

Abstract:
UNASSIGNED: 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.
UNASSIGNED: 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 (CD3+CD4+CXCR5+) and cTph (CD3+CD4+CXCR5-PD-1hi) cells..
UNASSIGNED: Flow cytometric analysis showed increased fractions of activated cTfh subsets including ICOS+ and ICOS+PD-1+ expressing cells, in patients compared to controls. Biologic blocking of IL-17A diminished the cTfh population. Furthermore, ICOS+ and ICOS+PD-1+ sub-populations were also inhibited. Finally, the cTph cell fraction significantly decreased after three months of successful treatment with biologics.
UNASSIGNED: Early anti-IL-17-mediated clinical remission in Ps is associated with decreased cTfh and cTph cell subpopulations.
摘要:
循环滤泡辅助性T细胞(cTfh)和循环外周辅助性T细胞(cTph)(其与cTfh群体具有共同特征)与免疫介导的和自身免疫性疾病如银屑病(Ps)的发病机理有关。它们与白细胞介素17(IL-17)轴的紧密相互作用以及用于治疗Ps的靶向IL-17的生物制剂的离体作用难以捉摸。这项研究旨在研究靶向IL-17的生物制剂对从P患者血液中分离的cTfh和cTph细胞亚群的影响。
在治疗开始和三个月后,从P患者中分离出外周血单核细胞(PBMC)。还从对照收集样品。使用单克隆抗体对细胞进行染色。流式细胞术评估cTfh(CD3+CD4+CXCR5+)和cTph(CD3+CD4+CXCR5-PD-1hi)细胞的分数。.
流式细胞术分析显示,包括ICOS+和ICOS+PD-1+表达细胞的活化cTfh亚群分数增加,与对照组相比,患者。IL-17A的生物阻断减少了cTfh群体。此外,ICOS+和ICOS+PD-1+亚群也被抑制。最后,cTph细胞分数在生物制剂成功治疗3个月后显著下降.
早期抗IL-17介导的Ps临床缓解与cTfh和cTph细胞亚群减少相关。
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