Mattos Rafael T, Medeiros Nayara I, Menezes Carlos A, Fares Rafaelle C G, Franco Eliza P, Dutra Walderez O, Rios-Santos Fabrício, Correa-Oliveira Rodrigo, Gomes Juliana A S
Laboratório de Biologia das Interações Celulares, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
Laboratório de Imunologia Celular e Molecular, Centro de Pesquisa René Rachou, FIOCRUZ, Belo Horizonte, MG, Brasil.
PLoS One. 2016 Dec 15;11(12):e0168610. doi: 10.1371/journal.pone.0168610. eCollection 2016.
Chronic low-grade inflammation is related to the development of comorbidities and poor prognosis in obesity. Monocytes are main sources of cytokines and play a pivotal role in inflammation. We evaluated monocyte frequency, phenotype and cytokine profile of monocyte subsets, to determine their association with the pathogenesis of childhood obesity. Children with obesity were evaluated for biochemical and anthropometric parameters. Monocyte subsets were characterized by flow cytometry, considering cytokine production and activation/recognition molecules. Correlation analysis between clinical parameters and immunological data delineated the monocytes contribution for low-grade inflammation. We observed a higher frequency of non-classical monocytes in the childhood obesity group (CO) than normal-weight group (NW). All subsets displayed higher TLR4 expression in CO, but their recognition and antigen presentation functions seem to be diminished due to lower expression of CD40, CD80/86 and HLA-DR. All subsets showed a lower expression of IL-10 in CO and correlation analyses showed changes in IL-10 expression profile. The lower expression of IL-10 may be decisive for the maintenance of the low-grade inflammation status in CO, especially for alterations in non-classical monocytes profile. These cells may contribute to supporting inflammation and loss of regulation in the immune response of children with obesity.
慢性低度炎症与肥胖症中共病的发生及不良预后相关。单核细胞是细胞因子的主要来源,在炎症中起关键作用。我们评估了单核细胞频率、单核细胞亚群的表型和细胞因子谱,以确定它们与儿童肥胖症发病机制的关联。对肥胖儿童进行了生化和人体测量参数评估。通过流式细胞术对单核细胞亚群进行表征,同时考虑细胞因子产生以及激活/识别分子。临床参数与免疫数据之间的相关性分析明确了单核细胞对低度炎症的作用。我们观察到,儿童肥胖组(CO)中非经典单核细胞的频率高于正常体重组(NW)。在CO组中,所有亚群的TLR4表达均较高,但由于CD40、CD80/86和HLA-DR表达较低,其识别和抗原呈递功能似乎有所减弱。在CO组中,所有亚群的IL-10表达均较低,相关性分析显示IL-10表达谱存在变化。IL-10的低表达可能对维持CO组中的低度炎症状态起决定性作用,尤其是对非经典单核细胞谱的改变而言。这些细胞可能有助于支持肥胖儿童免疫反应中的炎症和调节缺失。