IL-33 in obesity: where do we go from here?

IL-33 is a cytokine that belongs to the IL-1 family and is classically associated with type 2-like immune responses. In the adipose tissue, IL-33 is related to the beiging of adipocytes and to the maintenance of adipose tissue-resident immune cells, such as innate lymphoid cells 2, alternatively activated macrophages and regulatory T cells, which contribute to the maintenance of adipose tissue homeostasis. In the obese adipose tissue, the number of these cells is diminished, unlike the expression of IL-33, which is up-regulated. However, despite its increased expression, IL-33 is not able to maintain the homeostasis of the obese adipose tissue. IL-33 treatment, on the other hand, highly improves obesity-related inflammatory and metabolic alterations. The evidence that exogenous IL-33, but not adipose tissue-driven IL-33, regulates the inflammatory process in obesity leaves a gap in the understanding of IL-33 biology. Thus, in this review we discuss the potential mechanisms associated with the impaired action of IL-33 in obesity.