Associations between anthropometric parameters and immune-phenotypical characteristics of circulating Tregs and serum cytokines

Abstract

Objective: To investigate the associations between several anthropometric parameters and regulatory T cells (Tregs) and circulating cytokines in a population-based cohort.

Methods: Between 2018 and 2021, a total of 238 participants were examined up to three times within the scope of the MEGA study in Augsburg, Germany. Tregs were analyzed using flow cytometry and the serum concentrations of 52 cytokines were determined. Anthropometric parameters were measured, using also bioelectrical impedance analysis: body mass index (BMI), relative total body fat, relative visceral adipose tissue (rVAT), waist circumference (WC), waist-to-hip ratio (WHR) and body fat distribution. Associations were analyzed using linear mixed models with random intercept (Tregs) and conventional linear regression models (cytokines).

Results: WC and WHR were inversely associated with the general Treg subset. Four parameters (BMI, rVAT, WC, and WHR) were inversely associated with the conventional Treg population. Three cytokines showed a particularly strong association with several anthropometric parameters: the cutaneous T-cell attracting chemokine was inversely associated with anthropometric parameters, while hepatocyte growth factor and interleukine-18 showed positive associations.

Conclusions: Anthropometric measures are associated with Tregs and serum cytokine concentrations revealing new important interconnections between obesity and the adaptive immune system.

Keywords: BMI; Body fat; Cytokines; Flow cytometry; Regulatory T cells; Visceral fat.

Fig. 1

Gating strategy for the Treg panel. In the first step, T helper cells were identified by their expression of CD4. Then, different CD4 + T cell subsets were analyzed using the following antibodies: anti-CD25, anti-CD127, anti-CD45RA. The identified cell subsets were quantified by calculating their proportion of the parent gate cells

Fig. 2

Flow chart and time line of the included participants and measures for the analysis of Tregs (flow cytometry) and cytokines

Fig. 3

Associations between Treg subsets and anthropometric parameters. The figure displays the results of linear mixed models with random intercept and adjusted for sex, age, education, smoking status, alcohol consumption and hypothyroidism. Both, the exposure variables and the outcome were standardized. The results are presented on the right side (estimated β-coefficients with 95% CI, and FDR adjusted p values) and are graphically illustrated by the forest plot. The specific cell populations are shown on the left side and the respective parent gate is represented by the gray rectangles on the right edge of the figure

Fig. 4

Associations between anthropometric parameters and serum cytokine concentrations. The Linear regression models were adjusted for sex, age, education, smoking status, alcohol consumption, hypothyroidism and corresponding visit (baseline, follow-up). Both, the exposure variables and the outcome were standardized. The figure displays the estimated β-coefficients (X-axis) and the − log₁₀ transformed FDR-adjusted p values (Y-axis)