Dysregulation of circulating CD4+CXCR5+ T cells in type 2 diabetes mellitus

Abstract

Type 2 diabetes mellitus (T2DM) is characterized by a chronic low-grade inflammatory state. Follicular helper T cells (Tfh) play critical roles in inducing B-cell activation and producing various cytokines, whereas circulating CD4+CXCR5+ T cells (CTfh) may act as a counterpart to measure Tfh cell disorders. In this study, we investigated whether Tfh could be involved in the development of T2DM by assessing CTfh in peripheral blood. CTfh and it subtypes were determined by measuring CD3, CD4, CXCR5, CXCR3, and CCR6 in 68 T2DM patients and 60 healthy controls using flow cytometry. Results showed that proportion of CTfh in the peripheral CD4+ T cells was significantly increased in T2DM patients (8.5 ± 0.5%) than in controls (4.5 ± 0.3%) (p < 0.001). Further study revealed that the balance of CTfh subtypes was greatly dysregulated, in which percentage of Th17 subtype was significantly increased in patients. Investigating the correlation between CTfh and risk factors of T2DM demonstrated that proportion of CTfh were significantly elevated in patients with body mass index (BMI) over 24.0 (p = 0.005). Interestingly, patients with abdominal obesity had further increase in CTfh than those without abdominal obesity. This study suggests the involvement of CTfh in T2DM, especially in T2DM-related obesity.

Adaptive Immunity and Antigen‐Specific Activation in Obesity‐Associated Insulin Resistance

“…Follicular B cells contributed the bulk of the IL-6 and IL-10 secreted by total B cells with marginal zone B cells contributing very little of either cytokine [86]. Circulating follicular T helper cells (CD4+ CXCR5+), which provide assistance to B cells, were also found to be increased in diabetic patients versus healthy controls [87]. …”

T cell immunoglobulin and mucin domain‐containing molecule 3 on CD14+ monocytes serves as a novel biological marker for diabetes duration in type 2 diabetes mellitus

“…Based on the evidence that the circulating CD4 + T cells play important roles in type 2 diabetes, we first analyzed the expression of Tim‐3 on peripheral CD4 + T cells in both the healthy donors and the type 2 diabetes patients by flow cytometry. As shown in Figure a, the type 2 diabetes patients ( n = 31, 17.26 ± 1.51%) have a much higher level of Tim‐3 on CD4 + T cells than healthy donors ( n = 18, 4.69 ± 0.45%).…”

“…M2 macrophages carry out tissue surveillance and remodeling functions, and are associated with maintaining insulin sensitivity 39 . Tim-3 promotes the macrophages to polarize to the M2 phenotype 28 . The results of the present study showed that type 2 diabetes patients have a much lower level of Tim-3 on monocytes (Figure 1a).…”

Publication trends of research on diabetes mellitus and T cells (1997–2016): A 20-year bibliometric study

“…However, recent research has shown that T cells also play an important role in various steps in the development of T2DM. Dysregulation of CD4+CXCR5+ T cells and production of excessive proinflammatory cytokines may play an important part in the mechanism of chronic low-grade inflammation of insulin resistance[ 4 , 23 ]. The increased risk of T2DM due to TCR repertoire variation also implicates a role for autoimmunity[ 24 ].…”