Role of innate and adaptive immunity in obesity-associated metabolic disease

Abstract

Chronic inflammation in adipose tissue, possibly related to adipose cell hypertrophy, hypoxia, and/or intestinal leakage of bacteria and their metabolic products, likely plays a critical role in the development of obesity-associated insulin resistance (IR). Cells of both the innate and adaptive immune system residing in adipose tissues, as well as in the intestine, participate in this process. Thus, M1 macrophages, IFN-γ-secreting Th1 cells, CD8+ T cells, and B cells promote IR, in part through secretion of proinflammatory cytokines. Conversely, eosinophils, Th2 T cells, type 2 innate lymphoid cells, and possibly Foxp3+ Tregs protect against IR through local control of inflammation.

Figure 1. Changes in immune cell content and function in AT in lean versus obese settings influence IR.

In lean AT, immune cells play a predominant role in maintaining an antiinflammatory environment. For example, Th2 cells produce antiinflammatory cytokines including IL-4 and IL-10, which promote M2 macrophage polarization, and B cells produce IgM, which produces antiinflammatory IgM. During the course of obesity, significant changes in immune cell content and function occur that promote inflammation. Accumulation of M1 macrophages and Th1 cells results in excess production of proinflammatory cytokines including IFN-γ and TNF-α, and B cells undergo a class-switch, producing IgG.