Vollmer Carolina M, Dias Aleida S O, Lopes Lana M, Kasahara Taissa M, Delphim Letícia, Silva Júlio Cesar C, Lourenço Lucas Paulo, Gonçalves Hilary Cesário, Linhares Ulisses C, Gupta Sudhir, Bento Cleonice A M
Department of Microbiology and Parasitology Federal University of the State of Rio de Janeiro Rio de Janeiro Brazil.
Post-graduate Program in Microbiology University of the State of Rio de Janeiro Rio de Janeiro Brazil.
Clin Transl Allergy. 2022 Jun 14;12(6):e12153. doi: 10.1002/clt2.12153. eCollection 2022 Jun.
Obesity has often been associated with severe allergic asthma (AA). Here, we analyzed the frequency of different circulating CD4T-cell subsets from lean, overweight and obese AA patients.
Mononuclear cells from peripheral blood were obtained from 60 AA patients and the frequency of different CD4T-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.
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.
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 CD4T cell subsets, being adverse effects probably mediated by leptin overproduction.
肥胖常与重度过敏性哮喘（AA）相关。在此，我们分析了体重正常、超重和肥胖的AA患者中不同循环CD4T细胞亚群的频率。
从60例AA患者外周血中获取单核细胞，通过细胞计数法测定不同CD4T细胞亚群和1型调节性B细胞（Br1）的频率。分别通过酶联免疫吸附测定（ELISA）和3H胸苷摄取评估肥胖相关瘦素剂量对AA来源的CD4 T细胞培养物中细胞因子产生和调节性T细胞（Treg）功能的影响。通过ELISA对血浆中的瘦素水平进行定量。根据体重指数（BMI），将患者分为体重正常、超重和肥胖组。
AA的严重程度，主要在肥胖患者中，与混合Th2/Th17和Th17样细胞的扩增有关，而非经典的Th2样细胞。另一方面，重度AA患者中Th1样细胞、Br1细胞和调节性CD4 T细胞亚群的频率较低。虽然混合Th2/Th17表型和Th17样细胞的百分比与瘦素水平呈正相关，但调节性CD4 T细胞亚群和Br1细胞的频率与这种脂肪因子呈负相关。有趣的是，肥胖相关的瘦素剂量不仅提高了Th2和Th17细胞因子水平，还直接降低了体重正常的AA患者CD4 T细胞培养物中的Treg功能。
总之，我们的结果表明，肥胖可能通过促进Th17样细胞和Th2/Th17细胞的扩增以及减少调节性CD4T细胞亚群来增加AA的严重程度，这些不利影响可能是由瘦素过量产生介导的。
