LIGHT/TNFSF14 enhances adipose tissue inflammatory responses through its interaction with HVEM

Obesity-induced adipose tissue inflammation is characterized by increased macrophage infiltration and cytokine production, and is associated with metabolic disorders. LIGHT/TNFSF14, a member of the TNF superfamily, plays a role in the development of various inflammatory diseases. The purpose of this study was to examine the involvement of soluble LIGHT (sLIGHT) in obesity-induced adipose tissue inflammatory responses. LIGHT gene expression on macrophages/adipocytes was upregulated by treatment with obesity-related factors. sLIGHT displayed chemotactic activity for macrophages and T cells, and enhanced inflammatory cytokine release from macrophages, adipocytes, and adipose tissue-derived SVF cells. The sLIGHT-induced inflammatory responses were blunted by neutralizing anti-HVEM antibody or knockout of HVEM, a receptor for sLIGHT. These findings indicate that sLIGHT enhances adipose tissue inflammatory responses through its interaction with HVEM.