Adipose Tissue Immunomodulation and Treg/Th17 Imbalance in the Impaired Glucose Metabolism of Children with Obesity

Abstract

In the last few decades, obesity has increased dramatically in pediatric patients. Obesity is a chronic disease correlated with systemic inflammation, characterized by the presence of CD4 and CD8 T cell infiltration and modified immune response, which contributes to the development of obesity related diseases and metabolic disorders, including impaired glucose metabolism. In particular, Treg and Th17 cells are dynamically balanced under healthy conditions, but imbalance occurs in inflammatory and pathological states, such as obesity. Some studies demonstrated that peripheral Treg and Th17 cells exhibit increased imbalance with worsening of glucose metabolic dysfunction, already in children with obesity. In this review, we considered the role of adipose tissue immunomodulation and the potential role played by Treg/T17 imbalance on the impaired glucose metabolism in pediatric obesity. In the patient care, immune monitoring could play an important role to define preventive strategies of pediatric metabolic disease treatments.

Pediatric Obesity-Related Asthma: The Role of Nutrition and Nutrients in Prevention and Treatment

“…When the deposition of excessive adipose tissue occurs, the pathological immune system is activated, provoking a chronic low-grade inflammatory condition called "metainflammation" [7,[78][79][80], which plays a major part in the association between obesity and its multiple complications, including cardiovascular diseases, diabetes, dyslipidemia, and respiratory sequelae such as asthma [80][81][82].…”

“…We can divide macrophages into two main subtypes according to their secreted cytokines: M1, with a proinflammatory role, and M2, with an anti-inflammatory role [87]. The nutritional status causes changes in macrophage polarization in adipose tissue, with the M2 phenotype prevailing in lean children and M1 in those with excessive body weight [17,80]. M1 macrophages are defined by the expression of TNF alpha and inducible nitric oxide synthase, primarily expressed in visceral adipose tissue (VAT) and involved in the inflammatory response.…”

“…CD4+ T lymphocytes can be divided into T helper subsets Th1, Th2, Th17, and Treg, which differ in their surface markers, types of secreted cytokines, and cellular targets [91]. Several studies have observed that in an inflammatory condition, which is obesity-related chronic low-grade inflammation, there is a rise of circulating Th17 and Tregs [80,92,93]. Th17 lymphocytes are relevant in both innate and adaptive immunity.…”

“…On the other hand, Treg cells are abundant in lean adipose tissue and are involved in the regulation of autoimmunity, allergy, microbial infection, and oncogenesis, playing an important role in the maintenance of tissue homeostasis [88,89]. Treg lymphocytes increase in an inflammatory state, and in adipose tissue, interact with macrophages, preventing metabolic diseases and reducing local inflammation [80]. In addition, the functions of Treg and M1 macrophages are antagonistic; thus, their imbalance is a critical contributory factor in obesity [80,95,96].…”

“…Treg lymphocytes increase in an inflammatory state, and in adipose tissue, interact with macrophages, preventing metabolic diseases and reducing local inflammation [80]. In addition, the functions of Treg and M1 macrophages are antagonistic; thus, their imbalance is a critical contributory factor in obesity [80,95,96]. Th17/Treg imbalance, with increased Th17 and reduced Treg, can mediate the occurrence of obesity-related inflammation and metabolic disorders [97].…”