Leptin enhances TH2 and ILC2 responses in allergic airway disease

Abstract

Allergic asthma and obesity are the leading health problems in the world. Many studies have shown that obesity is a risk factor of development of asthma. However, the underlying mechanism has not been well established. In this study, we demonstrate that leptin, an adipokine elevated in obese individuals, promoted proliferation and survival of pro-allergic type 2 helper T cells and group 2 innate lymphoid cells and production of type 2 cytokines, which together contribute to allergic responses. Leptin activates mTORC1, MAPK, and STAT3 pathways in TH2 cells. The effects of leptin on TH2 cell proliferation, survival, and cytokine production are dependent on the mTORC1 and MAPK pathways as revealed by specific inhibitors. In vivo, leptin-deficiency led to attenuated experimental allergic airway inflammation. Our results thus support that obesity-associated elevation of leptin contributes to the increased susceptibility of asthma via modulation of pro-allergic lymphocyte responses.