It was shown that TSG-6 inhibited activation of antigen-presenting cells and T cells in a CD44 dependent manner, consequently blocking insulitis within the pancreas and delaying the onset of type 1 diabetes.235 Similarly, TSG-6 reduces the TLR2/NF-κB signaling in resident macrophages in the mouse model of peritonitis through CD44.225 In addition, cell-to-cell contact with M1 macrophages enhanced the TSG-6 paracrine production by MSCs, which become more potent in regulating immune cells.236 Therefore, MSCs rely on TSG-6 to survive in transplantation and to remodel the inflammatory environment. The gene discussed is TNFAIP6; the disease is type 1 diabetes mellitus.