Leptin favors Th17/Treg cell subsets imbalance associated with allergic asthma severity

Abstract

Background Obesity has often been associated with severe allergic asthma (AA). Here, we analyzed the frequency of different circulating CD4+T‐cell subsets from lean, overweight and obese AA patients. Methods Mononuclear cells from peripheral blood were obtained from 60 AA patients and the frequency of different CD4+T‐cell subsets and type 1 regulatory B cells (Br1) was determined by cytometry. The effect of obese‐related leptin dose on cytokine production and Treg cell function in AA‐derived CD4+ T cell cultures was evaluated by ELISA and 3H thymidine uptake, respectively. Leptin levels were quantified in the plasma by ELISA. According to the BMI, patients were stratified as lean, overweight and obese. Results AA severity, mainly among obese patients, was associated with an expansion of hybrid Th2/Th17 and Th17‐like cells rather than classic Th2‐like cells. On the other hand, the frequencies of Th1‐like, Br1 cells and regulatory CD4+ T‐cell subsets were lower in patients with severe AA. While percentages of the hybrid Th2/Th17 phenotype and Th17‐like cells positively correlated with leptin levels, the frequencies of regulatory CD4+ T‐cell subsets and Br1 cells negatively correlated with this adipokine. Interestingly, the obesity‐related leptin dose not only elevated Th2 and Th17 cytokine levels, but also directly reduced the Treg function in CD4+ T cell cultures from lean AA patients. Conclusion In summary, our results indicated that obesity might increase AA severity by favoring the expansion of Th17‐like and Th2/Th17 cells and decreasing regulatory CD4+T cell subsets, being adverse effects probably mediated by leptin overproduction.

The Role of Adipokines in the Pathogenesis of Psoriasis

“…De Rosa and colleagues demonstrated that neutralizing leptin monoclonal antibodies enhances the proliferation of Tregs [ 160 ]. Furthermore, leptin decreases IL-10 production from CD4+ T cells from patients with asthma [ 161 ]. In line with previous findings, Wang et al showed that leptin receptor antagonist promotes Foxp3 and inhibits IL-17 in the thyroid gland of a mouse model with experimental autoimmune thyroiditis [ 162 ].…”

Leptin and Asthma: What Are the Interactive Correlations?

“…Leptin also activates pro-inflammatory Th17 cells [ 124 ]. Leptin elevated Th17 cytokine levels while reducing the function of Treg cells in the culture of CD4 + T cells from lean allergic-asthma patients [ 121 , 125 ]. Leptin shifts T-helper (Th) cells to Th1 cells by producing IFN-γ [ 126 ].…”

Role of Leptin as a Link between Asthma and Obesity: A Systematic Review and Meta-Analysis

“…Adipose tissue has endocrine functions and promotes a cascade of pro-inflammatory cytokines and adipokines, including leptin, which may be a key factor in the pathology of asthma [27,37,38]; this is because the adipokine may induce changes in the mechanics and functions of the lungs via bronchial inflammation on admission, compared to the stable phase of the disease [42][43][44], mainly due to the accumulation of leptin-producing monocytes in the airway [45]. These ultimately favor the expansion in Th17 cells and the decrease in regulatory T cells [46]. In addition, leptin has been suggested to promote airway inflammation via upregulation of the mitochondrial reactive oxygen species/NOD-, LRR-, and the pyrin domain-containing protein 3 (mostly known as mtROS/NLRP3) inflammasome signaling pathway in human normal BEAS-2 bronchial epithelial cells in vitro [47].…”