Dataset Information

Variation in IL-21-secreting circulating follicular helper T cells in Kawasaki disease.

ABSTRACT:

Objective

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.

Methods

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.

Results

In the acute phase (AP), the percentages of ICOS^highPD-1^high, ICOS⁺PD-1⁺, ICOS^-PD-1⁺, CD45RA^-IL-21⁺ cTfh cells and serum IL-21 levels significantly increased. Furthermore, the percentages of ICOS^highPD-1^high 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⁺, ICOS^highPD-1^high 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⁺, ICOS^highPD-1^high, 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.

Conclusions

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.

SUBMITTER: Xu M

PROVIDER: S-EPMC6307283 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Publications

Variation in IL-21-secreting circulating follicular helper T cells in Kawasaki disease.

Xu Meng M Jiang Yanfang Y Zhang Jian J Zheng Yan Y Liu Deying D Guo Lishuang L Yang Sirui S

BMC immunology 20181227 1

<h4>Objective</h4>Circulating follicular helper T (cTfh) cells are a specialized subset of CD4<sup>+</sup> 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 (K ...[more]

PMID: 30587125

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Project description:To assess circulating follicular helper T (Tfh)-like CD4+ T cells in patients with systemic lupus erythematosus (SLE) and determine their relationship to disease activity.Blood samples from patients with SLE, as well as blood samples from patients with Behçet's disease (BD) and healthy individuals as controls, were analyzed. In all samples, circulating Tfh-like cells were enumerated by flow cytometry, using, as markers, expression of CXCR5, inducible T cell costimulator (ICOS), and programmed death 1 (PD-1) protein, as well as secretion of interleukin-21 (IL-21). The frequency of circulating Tfh-like cells was compared to that of circulating plasmablasts (CD19+IgD-CD38+). In addition, the possible association of circulating Tfh-like cells with the SLE Disease Activity Index (SLEDAI) was evaluated.The subset of circulating Tfh-like T cells, identified as CXCR5(high) ICOS(high) PD-1(high) , was expanded in the blood of SLE patients compared to controls. Circulating Tfh-like cells were found to produce IL-21 and had lower expression of CCR7 as compared to that in circulating CXCR5(high) central memory T cells, thereby enabling their distinction. Expression of PD-1, but not ICOS or CXCR5, was significantly elevated in circulating Tfh-like cells from SLE patients compared to controls. PD-1 expression among CXCR5(high) circulating Tfh-like cells correlated with the SLEDAI, frequency of circulating plasmablasts, and anti-double-stranded DNA antibody positivity, but not with disease duration or past organ injury; rather, this cell profile appeared to be a reflection of current active disease.Circulating Tfh-like cells are associated with disease activity in SLE, suggesting that their presence indicates abnormal homeostasis of T cell-B cell collaboration, with a causal relationship that is central to disease pathogenesis. These findings also suggest that circulating Tfh-like cells provide a surrogate for aberrant germinal center activity in SLE, and that their PD-1 expression offers a tool for measuring disease activity and monitoring the response to therapies.

Dataset Information

Variation in IL-21-secreting circulating follicular helper T cells in Kawasaki disease.

Objective

Methods

Results

Conclusions

Publications

Variation in IL-21-secreting circulating follicular helper T cells in Kawasaki disease.

Similar Datasets

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