Innate lymphoid cells type 2 - emerging immune regulators of obesity and atherosclerosis

The low-grade inflammation present in obese visceral adipose tissue impairs glucose metabolism, and contributes to the development of insulin resistance and weight gain. Immune processes occurring in response to the deposition of cholesterol within the vascular walls support atherosclerotic plaque growth and contribute to the cardiovascular complications. In both the obese adipose tissue and the atherosclerotic plaque, the Th1-type immune environment dominates over the Th2/Treg-type due to the overproduction of pro-inflammatory cytokines (IFN-γ, IL-6, TNF-α) and the deficiency of Th2-type processes and interleukins (IL-4, IL-5, IL-10, IL-13). So far, Th2 cells and eosinophils have been considered as the main providers of Th2-type mediators and the basis of Th2-type immunity in tissues. However, recently discovered innate lymphoid type 2 cells (ILC2s), which infiltrate lean visceral adipose tissue and the vascular wall, are believed to orchestrate local Th2-like immune responses. Upon activation by tissue-derived IL-33 and IL-25, ILCs2 secrete mostly IL-4, IL-5, IL-9 and IL-13: cytokines responsible for the accumulation of eosinophils and polarization of alternatively-activated macrophages, which altogether create the beneficial anti-inflammatory and metabo-regulatory environment in the adipose tissue and the vascular wall. Consequently, ILC2s-orchestrated immune environment seems to prevent obesity and atherosclerosis. Thus, ILCs2 appear to be the emerging immune regulators of immune and metabolic homeostasis in both adipose tissue and the vascular wall.