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

Abstract

ObjectiveCirculating 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.MethodsAccording 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.ResultsIn 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.ConclusionsThe 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.Electronic supplementary materialThe online version of this article (10.1186/s12865-018-0282-8) contains supplementary material, which is available to authorized users.

Distinct variations of antibody secreting cells and memory B cells during the course of Kawasaki disease

“…Recently, researchers found the increased percentage as well as absolute number of CD19+ cells in the peripheral blood of patients with KD [12]. In addition to these direct evidence, our latest study presented an increased level of one activated subset of T follicular helper cells and serum IL-21 [13, 14], which are vital to B-cell proliferation and differentiation [15], strongly suggesting the involvement of humoral immunity in KD. Moreover, with the development of genomics, susceptible genes associated with B cells have also been identified [16].…”

“…One of the advantages for the differentiation of B cells into ASCs may be the elevation of B-cell-activating factor (BAFF), which can effectively promote the proliferation, differentiation, and survival of B cells [31]. Another superiority for ASCs is the increased levels of cytokines, such as IL-6, IL-17 and IL-21 [13, 32, 33]. Furthermore, increased expression of CD138 is capable of promoting the maturation, accumulation and particularly, survival of ASCs upon IL-6 signaling [34].…”

Peripheral follicular cytotoxic T -like cells in Kawasaki disease with coronary artery aneurysms

“…[ 7 ] Furthermore, according to our previous studies that included 24 KD patients without coronary involvement and 20 healthy controls, the percentages of CD4 negative subpopulation were 6.45% (2.99–14.5) and 6.87% (2.6–10.3), respectively, of circulating CXCR5+ T cells. [ 8 ] Thus, we believe that the levels of Tfc-like cells of the 2 patients in the acute stage are affirmatively increased.…”

Frequency of Efficient Circulating Follicular Helper T Cells Correlates with Dyslipidemia and WBC Count in Atherosclerosis

“…A recent study showed that in patients with myositis, IL-21 expressing CCR7 lo PD-1 hi efficient cTfh cells significantly increased, and the frequencies of these cells had a correlation with the disease progression [ 28 ] . Moreover, the percentage of ICOS hi PD-1 hi efficient cells was higher in patients with Kawasaki syndrome [ 29 ] . The ICOS + PD-1 + cTfh cells and IL-21 producing CD4 + CXCR5 + PD-1 + T cells were also shown to be significantly higher in patients with Sjögren syndrome [ 30 ] .…”