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

Meng Xu; Yanfang Jiang; Jian Zhang; Yan Zheng; Deying Liu; Lishuang Guo; Sirui Yang

doi:10.1186/s12865-018-0282-8

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

BMC Immunol. 2018 Dec 27;19(1):43. doi: 10.1186/s12865-018-0282-8.

Authors

Meng Xu¹, Yanfang Jiang^{2

3

4}, Jian Zhang⁵, Yan Zheng⁵, Deying Liu⁶, Lishuang Guo¹, Sirui Yang⁷

Affiliations

¹ Department of Pediatric Rheumatology and Allergy, The First Hospital of Jilin University, Changchun, 130021, China.
² Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, 130021, China.
³ Key Laboratory of Zoonoses Research, Ministry of Education, The First Hospital of Jilin University, Changchun, 130021, China.
⁴ Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, China.
⁵ Department of Pediatric, Children's Hospital, Changchun, 130021, China.
⁶ Department of Pediatric Rheumatology and Immunology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430000, China.
⁷ Department of Pediatric Rheumatology and Allergy, The First Hospital of Jilin University, Changchun, 130021, China. sryang@jlu.edu.cn.

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.

Keywords: Circulating follicular helper T cells; Immune response; Interleukin-21; Kawasaki disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Child, Preschool
Female
Humans
Infant
Interleukins / blood*
Male
Mucocutaneous Lymph Node Syndrome / immunology*
Receptors, CXCR5 / immunology
T-Lymphocytes, Helper-Inducer / cytology
T-Lymphocytes, Helper-Inducer / immunology*

Substances

Interleukins
Receptors, CXCR5
interleukin-21