Zhao Ruxing, Tang Dongqi, Yi Shounan, Li Wenjuan, Wu Chuanlong, Lu Yiran, Hou Xinguo, Song Jun, Lin Peng, Chen Li, Sun Lei
Department of Endocrinology, Qilu Hospital, Shandong University, Jinan, China ; Institute of Endocrinology and Metabolism, Shandong University, Jinan, China ; Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China.
Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China.
PLoS One. 2014 Jan 17;9(1):e85770. doi: 10.1371/journal.pone.0085770. eCollection 2014.
Chronic low-grade inflammation has long been recognized as the central link between obesity and type 2 diabetes (T2D). The novel subset of T helper (Th) cells, Th22, plays an emerging role in chronic inflammation. We investigated the potential association between Th22 and the pathogenesis of obesity and T2D.
Ninety T2D inpatients (T2D group), 30 healthy participants with BMI ranged from 19 to 23.9 kg/m2 (CTL group) and 30 metabolically healthy obese controls with BMI ≥ 30 kg/m2 (MHO group) were employed in our study. Peripheral frequencies of Th22 and Th1 and Th17 cells were determined by flow cytometry based on their specific cytokine patterns. Cytokine levels in fresh plasma were quantified by ELISA.
Compared to that in CTL group (1.18±0.06%, n = 28), peripheral frequency of Th22 cells was significantly increased in MHO group (1.88±0.10%, n = 30) and in T2D group (2.247±0.10%, n = 89). There was a consistent notable increase in plasma interleukin (IL)-22 of T2D patients [47.56 (30.55-76.89) pg/mL] as compared with that of MHO group [36.65 (29.52-55.70) pg/ml; *P<0.0001] and CTLs [36.33 (31.93-40.62) pg/mL; *P<0.0001]. Furthermore, other than Th1/Th17, previously frequently described participants in obesity and T2D, there was a strong correlation between Th22 frequency and the homeostasis model of assessment for insulin resistance index (r = 0.6771, *P<0.0001) and HOMA for β-cell function (r = -0.7264, *P<0.0001).
There were increased Th22 frequencies and IL-22 levels in obesity and T2D. Elevated Th22 and IL-22 also aided in the differentiation of MHO from T2D patients. The notable correlation implied that Th22 might play a more determinant role in both insulin resistance and β-cell impairment.
长期以来,慢性低度炎症一直被认为是肥胖与2型糖尿病(T2D)之间的核心联系。新型辅助性T(Th)细胞亚群Th22在慢性炎症中发挥着越来越重要的作用。我们研究了Th22与肥胖及T2D发病机制之间的潜在关联。
本研究纳入了90例T2D住院患者(T2D组)、30例体重指数(BMI)在19至23.9 kg/m²之间的健康参与者(CTL组)和30例BMI≥30 kg/m²的代谢健康肥胖对照者(MHO组)。根据其特定的细胞因子模式,通过流式细胞术测定Th22以及Th1和Th17细胞的外周血频率。采用酶联免疫吸附测定法(ELISA)对新鲜血浆中的细胞因子水平进行定量分析。
与CTL组(1.18±0.06%,n = 28)相比,MHO组(1.88±0.10%,n = 30)和T2D组(2.247±0.10%,n = 89)中Th22细胞的外周血频率显著升高。与MHO组[36.65(29.52 - 55.70)pg/mL;*P<0.0001]和CTL组[36.33(31.93 - 40.62)pg/mL;*P<0.0001]相比,T2D患者血浆白细胞介素(IL)-22水平也持续显著升高[47.56(30.55 - 76.89)pg/mL]。此外,除了肥胖和T2D中先前经常描述的Th1/Th17外,Th22频率与胰岛素抵抗指数的稳态模型评估(r = 0.6771,*P<0.0001)以及β细胞功能的稳态模型评估(HOMA)(r = -0.7264,*P<0.0001)之间存在强相关性。
肥胖和T2D患者中Th22频率和IL-22水平升高。Th22和IL-22升高也有助于区分MHO与T2D患者。显著的相关性表明Th22可能在胰岛素抵抗和β细胞损伤中发挥更具决定性的作用。