A new Cutting Edge article, in the April 2013 issue of the Journal of Immunology, identifies a link between leptin and T helper (Th)17 cells, based on the evidence that leptin was able to promote Th17 responses in human CD4+ T cells and in mice, both in vitro and in vivo, by inducing the transcription of the Th17 master regulator RORγt.
Leptin, an adipokine that controls metabolism and energy expenditure, is a potent immune regulator through induction of TNF-α, IL-6 and IL-12 production, and an inhibitior of CD4+CD25+FOXP3+ regulatory T cells.
In this study, Yiyun Yu and colleagues from the Department of Medicine, University of California Los Angeles, Los Angeles, CA, found that in the presence of increasing concentrations of leptin, Th17 cell numbers increased in a dose-dependent manner in cultures of healthy human PBMC. Importantly, the researchers observed that leptin promoted Th17 differentiation by inducing RORγt (ROR nuclear hormone receptor family) transcription in CD4+ T cells.
Leptin also increased Th17 responses in (NZB × NZW)F1 lupus-prone mice, while the authors also report a positive correlation between plasma leptin and IL-17 in systemic lupus erythematosus (SLE) patients.
This study, along with previous research implicating leptin’s Th17-promoting effects in collagen-induced arthritis and Hashimoto’s thyroiditis, validates the link between adipokines, metabolism/nutrition and susceptibility to autoimmunity.