TNF and diabetes mellitus: As an inhibitory molecule, Tim-3 has been reported to promote immune tolerance through downregulation of Th1-dependent immune responses, and Tim-3 pathway blockade was shown to accelerate diabetes in non-obese diabetic mice (47) I contrast, and attesting to the obvious complexity of Tim-3 interactions in different immune cells, Tim-3 was shown to promote macrophage activation through the NF-κB/TNF-α pathway to exacerbate foot cell injury in diabetic nephropathy (48).