Syndecan-1 controls the role of iNKT cells in regulating body fat mass and glucose homeostasis in mice

Abstract

Abstract Obesity is a major risk factor for metabolic disease, with white adipose tissue inflammation emerging as a key underlying pathology that coupled with insulin resistance, type 2 diabetes and cardiovascular diseases. Immune cells play a central role in maintaining immune homeostasis of these adipose tissues. Formerly, significant efforts have been made in understanding the roles of conventional and regulatory T cells. Natural killer T17 cells (NKT17 cells) are lipid-sensing innate T cells, restricted by the antigen-presenting molecule CD1d and express the transcription factor RORyt. Though, the role of invariant natural killer T (iNKT) cells is still remains unclear. Recently, we have discovered that syndecan-1 (sdc1) highly express on the surface of NKT17 cells. After thymus, sdc1-expressing NKT17 cells specifically localize the adipose tissues. Encouraged with previous results, iNKT cells were characterized in both wild type (wt) and sdc1 knock out (sdc1ko) BALB/c mice. The iNKT cells with sdc-1ko mice have shown higher level of proliferation compared to wt. The proliferation assay has shown significantly high number of iNKT cells in S-phase of cell cycle dominating with double positive (CD4+CD8+T cells) T cells in sdc1ko mice. Further, sdc-1ko mice have significantly reduced body fat and improved glucose tolerance. Future study with siRNA, targeting sdc1 in iNKT cells could be a contributing factor in regulating obesity and glucose homeostasis and to understand the physiological significance of sdc1 expression by NKT17 cells. Thus, developing the strategies that maintain immune homeostasis in obese adipose tissue could lead to novel therapeutics that improve and/or prevent the metabolic and cardiovascular risks of obesity.