Therapeutic Perspectives of CD26 Inhibitors in Imune-Mediated Diseases

Abstract

The enzymatic activity of CD26/DPP4 (dipeptidyl peptidase 4/DPP4) is highlighted in multiple studies to play a vital role in glucose metabolism by cleaving and inactivating the incretins glucagon-like peptide-1 (GLP) and gastric inhibitory protein (GIP). A large number of studies demonstrate that CD26 also plays an integral role in the immune system, particularly in T cell activation. CD26 is extensively expressed in immune cells, such as T cells, B cells, NK cells, dendritic cells, and macrophages. The enzymatic activity of CD26 cleaves and regulates numerous chomokines and cytokines. CD26 inhibitors have been widely used for the treatment of diabetes mellitus, while it is still under investigation as a therapy for immune-mediated diseases. In addition, CD26’s involvement in cancer immunology was also described. The review aims to summarize the therapeutic effects of CD26 inhibitors on immune-mediated diseases, as well as the mechanisms that underpin them.

Identification of Novel Biomarkers of Spinal Muscular Atrophy and Therapeutic Response by Proteomic and Metabolomic Profiling of Human Biological Fluid Samples

“…DPP4 acts also on incretins such as GLP-1, which are essential for controlling blood sugar levels. Currently, CD26 inhibitors are being investigated as potential therapeutics for diabetes mellitus, immune-mediated diseases, and cancer [35].…”

Immunomodulatory activity of dipeptidyl peptidase‐4 inhibitors in immune‐related diseases

“…Due to its widespread distribution, clinical and experimental research over the past 30 years has suggested that the DPP‐4/CD26 pathway is involved in various pathological processes and diseases of the immune system, which correlates with their severity [2, 13, 16]. Most results for non‐diabetic effects caused by DPP‐4i therapy in patients currently point to generally positive side effects.…”

“…sDPP-4/CD26 remains enzymatically # First-time first author: Marija Drakul active with the ability to regulate numerous functions, including those related to the immune system [8,12]. In numerous immune-mediated diseases (such as rheumatoid arthritis, type 1 diabetes, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease), an altered DPP-4/CD26 enzyme activity was noted [13].…”

“…These drugs have a low risk of hypoglycemia, medium to high selectivity, and are well absorbed. They are moderately metabolized and are mainly eliminated through the kidneys or hepatobiliary tract (linagliptin) [13,16].…”

Effect of DPP4/CD26 expression on SARS‑CoV‑2 susceptibility, immune response, adenosine (derivatives m62A and CD) regulations on patients with cancer and healthy individuals

“…In addition, clinical trials and preclinical studies have evaluated the efficacy and safety of DPP4 inhibitors in immune-mediated disorders and anti-cancer immune responses ( 14 ). It is thought that these inhibitors may act by regulating the balance of the T helper 1/2 (Th1/Th2) phenotype and production of cytokines ( 15 , 16 ). Over-expression of DPP4 in lung diseases may increase the susceptibility to viral invasion.…”