Crosstalk between adipocytes and immune cells in adipose tissue inflammation and metabolic dysregulation in obesity

Abstract

Recent findings, notably on adipokines and adipose tissue inflammation, have revised the concept of adipose tissues being a mere storage depot for body energy. Instead, adipose tissues are emerging as endocrine and immunologically active organs with multiple effects on the regulation of systemic energy homeostasis. Notably, compared with other metabolic organs such as liver and muscle, various inflammatory responses are dynamically regulated in adipose tissues and most of the immune cells in adipose tissues are involved in obesity-mediated metabolic complications, including insulin resistance. Here, we summarize recent findings on the key roles of innate (neutrophils, macrophages, mast cells, eosinophils) and adaptive (regulatory T cells, type 1 helper T cells, CD8 T cells, B cells) immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. In particular, the roles of natural killer T cells, one type of innate lymphocyte, in adipose tissue inflammation will be discussed. Finally, a new role of adipocytes as antigen presenting cells to modulate T cell activity and subsequent adipose tissue inflammation will be proposed.

Fig. 1

Interactions of adipose tissue immune cells. In lean adipose tissue, IL-4 secreted by eosinophils and Th2 cells activates M2 type macrophages, which express arginase and anti-inflammatory cytokines such as IL-10. Regulatory T (Treg) cells also play an important role in anti-inflammatory responses via cell-cell contact or cytokine secretion involving IL-10. However, in obese adipose tissue the number of pro-inflammatory immune cells is increased and that of anti-inflammatory immune cells is decreased. Neutrophils, which are early responders to inflammatory responses, infiltrate the adipose tissue where they secrete elastase and also stimulate M1 type macrophage infiltration and pro-inflammatory cytokine secretion. In addition, levels of IFN-γ-secreting cell types, such as Th1 cells, CD8 T cells, and mast cells, are elevated in obese adipose tissue. B cells also play a pro-inflammatory role through secretion of obesity-induced IgG.

Fig. 2

Model of adipocytes as antigen presenting cells. Adipocytes could act as antigen presenting cells via expression of key molecules for antigen presentation in obese adipose tissue. Adipocytes expressing MHC I could mediate CD8 T cell responses whereas those expressing MHC II molecules could regulate CD4 T cell responses. In addition, adipocytes could modulate the function and activation of iNKT cells via high expression of CD1d molecules in adipose tissue.