Table 1.

The immunoregulation effects of CD26 inhibitors.

Immune-Mediated Disease	CD26 Inhibitor	Mechanism of the Effects	Ref.
Diabetic Cardiovascular Disease	Alogliptin	Inhibits IL-1 and TLR4-mediated IL-6 expression, as well as reducing cholesterol and triglycerides, decelerating atherosclerosis	[9]
	Linagliptin	Inhibited effects on xanthine oxidase.	[10]
	Saxagliptin	Reduced CD40 expression in inflammatory monocytes and macrophages implicated in the initiation of atherosclerosis	[11]
	Sitagliptin	Stimulates the adenosine monophosphate-activated protein kinase (AMPK) pathway and inhibits the mitogen-activated protein kinase (MAPK) pathway	[12]
	Teneligliptin	Suppression of CD36, acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1) gene expression partly by attenuating the harmful effects of advanced glycation end product (AGEs)	[13]
	Vildagliptin	Reduce the levels of LDL cholesterol, triglyceride, and free fatty acid and increase the levels of HDL cholesterol in patients with T2DM; Decreases infarct size is reduction in ROS production, given that mitochondrial dysfunction is caused by the extensive release of H2O2, as one of pro-oxidative markers	[14,15]
Autoimmune Diabetes	Sitagliptin	Unknown	[16]
	Linagliptin	Inhibits the CD26-mediated stimulation of autoimmune T-cell activation and islet infiltration	[17]
	Vildagliptin	Increase insulin secretion and decrease the extensive peri-insulitis which was mainly formed by CD3-positive T cells	[18]
	Saxagliptin	Unknown	[19]
Inflammatory Bowel Disease	Linagliptin	Inhibits the IL-6/JAK2/STAT3 pathway via downregulating p-JAK2/JAK2 and p-STAT3/STAT3 protein expression and HMGB1/RAGE/NF-κB cascade through lowering HMGB1, RAGE, and p-NF-κB p65/NF-κB	[20]
	Sitagliptin	Enhancement of GLP-2 action and the subsequent protective effects on intestinal barrier by inhibiting epithelial cells apoptosis and promoting their proliferation	[21]
	Anagliptin	Unknown	[22]
Graft-versus-Host Disease	Sitagliptin	Block T-cell activation, resulting in decreased secretion of pro-inflammatory cytokines; attenuate cleavage of CXCL12, facilitating the homing and engraftment of donor cells in patients undergoing hematopoietic stem cell transplantation	[23,24]
Coronavirus-related immunological response	Sitagliptin	Unknown	[25]
Multiple Sclerosis (MS)	Linagliptin	Showed neuroprotective properties against neurodegenerative diseases., exerted an anti-inflammatory effect in MS by reducing brain TNF-α	[26]