Circulating follicular helper T (cTfh) cells are a specialized subset of CD4+ T cells that express the CXC-chemokine receptor 5 (CXCR5). These cells exhibit immune activities by inducing B cell differentiation and proliferation via the secretion of interleukin (IL)-21. Multiple studies have demonstrated that cTfh cells are associated with the progression and severity of numerous diseases. To investigate the role of cTfh cells in the development of Kawasaki disease (KD), we analyzed the distinct subpopulations of cTfh cells and serum IL-21 levels in different phases of KD. According to the differential expression of inducible co-stimulator (ICOS) and programmed cell death protein 1 (PD-1), cTfh cells were divided into distinct subsets. We used flow cytometry and flow cytometric bead arrays (CBA) to analyze subsets of CD4+CXCR5+ T cells and serum IL-21 levels. The samples were collected from control subjects and Kawasaki disease patients in the acute and remission phases. In the acute phase (AP), the percentages of ICOShighPD-1high, ICOS+PD-1+, ICOS−PD-1+, CD45RA−IL-21+ cTfh cells and serum IL-21 levels significantly increased. Furthermore, the percentages of ICOShighPD-1high and ICOS+PD-1+ cTfh cells positively correlated with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values, whereas the percentage of ICOS−PD-1+ cTfh cells indicated negative correlations. The percentages of ICOS+PD-1+, ICOShighPD-1high and CD45RA−IL-21+ cTfh cells correlated positively with serum IL-21 levels. In the remission phase (RP), the percentages of ICOS−PD-1+, CD45RA−IL-21+ cTfh cells and serum IL-21 levels were significantly decreased. In contrast, the percentages of ICOS+PD-1+, ICOShighPD-1high, and ICOS+PD-1− cTfh cells were further increased. Among these subsets, only CD45RA−IL-21+ cTfh cells correlated positively with serum IL-21 levels. The present study is the first investigation that examined the distribution of circulating cTfh cell subsets in Kawasaki disease. Both cTfh cells and serum IL-21 are essential to the pathogenesis of KD. Our study provides further understanding of the immune response involved in KD and offers novel insights in the pathogenetic mechanism of this disease.

中文翻译：

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川崎病中分泌IL-21的循环性卵泡辅助性T细胞的变化

循环滤泡辅助性T（cTfh）细胞是表达CXC-趋化因子受体5（CXCR5）的CD4 + T细胞的专门子集。这些细胞通过分泌白介素（IL）-21诱导B细胞分化和增殖而表现出免疫活性。多项研究表明，cTfh细胞与多种疾病的进展和严重程度有关。为了研究cTfh细胞在川崎病（KD）发生中的作用，我们分析了KT不同阶段中cTfh细胞的不同亚群和血清IL-21水平。根据诱导型共刺激物（ICOS）和程序性细胞死亡蛋白1（PD-1）的差异表达，将cTfh细胞分为不同的亚组。我们使用流式细胞仪和流式细胞仪珠阵列（CBA）分析了CD4 + CXCR5 + T细胞的子集和血清IL-21水平。从急性期和缓解期的对照组和川崎病患者中收集样品。在急性期（AP），ICOShighPD-1high，ICOS + PD-1 +，ICOS-PD-1 +，CD45RA-IL-21 + cTfh细胞和血清IL-21水平的百分比显着增加。此外，ICOShighPD-1high和ICOS + PD-1 + cTfh细胞的百分比与红细胞沉降率（ESR）和C反应蛋白（CRP）值呈正相关，而ICOS-PD-1 + cTfh细胞的百分比则呈负相关相关性。ICOS + PD-1 +，ICOShighPD-1high和CD45RA-IL-21 + cTfh细胞的百分比与血清IL-21水平呈正相关。在缓解阶段（RP），ICOS-PD-1 +的百分比 CD45RA-IL-21 + cTfh细胞和血清IL-21水平显着降低。相反，ICOS + PD-1 +，ICOShighPD-1high和ICOS + PD-1- cTfh细胞的百分比进一步增加。在这些亚组中，只有CD45RA-IL-21 + cTfh细胞与血清IL-21水平呈正相关。本研究是首次调查川崎病中循环性cTfh细胞亚群分布的研究。cTfh细胞和血清IL-21对KD的发病机理均至关重要。我们的研究提供了对参与KD的免疫反应的进一步了解，并提供了对该疾病的致病机理的新颖见解。只有CD45RA-IL-21 + cTfh细胞与血清IL-21水平呈正相关。本研究是首次调查川崎病中循环性cTfh细胞亚群分布的研究。cTfh细胞和血清IL-21对KD的发病机理均至关重要。我们的研究提供了对参与KD的免疫反应的进一步了解，并提供了对该疾病的致病机理的新颖见解。只有CD45RA-IL-21 + cTfh细胞与血清IL-21水平呈正相关。本研究是首次调查川崎病中循环性cTfh细胞亚群分布的研究。cTfh细胞和血清IL-21对KD的发病机理均至关重要。我们的研究提供了对参与KD的免疫反应的进一步了解，并提供了对该疾病的致病机理的新颖见解。