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 st...

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Main Authors: Meng Xu, Yanfang Jiang, Jian Zhang, Yan Zheng, Deying Liu, Lishuang Guo, Sirui Yang
Format: Article
Language:English
Published: BMC 2018-12-01
Series:BMC Immunology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12865-018-0282-8
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author Meng Xu
Yanfang Jiang
Jian Zhang
Yan Zheng
Deying Liu
Lishuang Guo
Sirui Yang
author_facet Meng Xu
Yanfang Jiang
Jian Zhang
Yan Zheng
Deying Liu
Lishuang Guo
Sirui Yang
author_sort Meng Xu
collection DOAJ
description 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 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. 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.
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spelling doaj.art-c15b8736f8df4a7881b3311ba454b7f42022-12-22T02:44:22ZengBMCBMC Immunology1471-21722018-12-0119111010.1186/s12865-018-0282-8Variation in IL-21-secreting circulating follicular helper T cells in Kawasaki diseaseMeng Xu0Yanfang Jiang1Jian Zhang2Yan Zheng3Deying Liu4Lishuang Guo5Sirui Yang6Department of Pediatric Rheumatology and Allergy, The First Hospital of Jilin UniversityGenetic Diagnosis Center, The First Hospital of Jilin UniversityDepartment of Pediatric, Children’s HospitalDepartment of Pediatric, Children’s HospitalDepartment of Pediatric Rheumatology and Immunology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & TechnologyDepartment of Pediatric Rheumatology and Allergy, The First Hospital of Jilin UniversityDepartment of Pediatric Rheumatology and Allergy, The First Hospital of Jilin UniversityAbstract 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 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. 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.http://link.springer.com/article/10.1186/s12865-018-0282-8Circulating follicular helper T cellsKawasaki diseaseInterleukin-21Immune response
spellingShingle Meng Xu
Yanfang Jiang
Jian Zhang
Yan Zheng
Deying Liu
Lishuang Guo
Sirui Yang
Variation in IL-21-secreting circulating follicular helper T cells in Kawasaki disease
BMC Immunology
Circulating follicular helper T cells
Kawasaki disease
Interleukin-21
Immune response
title Variation in IL-21-secreting circulating follicular helper T cells in Kawasaki disease
title_full Variation in IL-21-secreting circulating follicular helper T cells in Kawasaki disease
title_fullStr Variation in IL-21-secreting circulating follicular helper T cells in Kawasaki disease
title_full_unstemmed Variation in IL-21-secreting circulating follicular helper T cells in Kawasaki disease
title_short Variation in IL-21-secreting circulating follicular helper T cells in Kawasaki disease
title_sort variation in il 21 secreting circulating follicular helper t cells in kawasaki disease
topic Circulating follicular helper T cells
Kawasaki disease
Interleukin-21
Immune response
url http://link.springer.com/article/10.1186/s12865-018-0282-8
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AT yanzheng variationinil21secretingcirculatingfollicularhelpertcellsinkawasakidisease
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