Immunological communication between SARS-CoV-2 and dipeptidyl peptidase- 4: a possible therapeutic strategy.

Immunological communication between SARS-CoV-2 and dipeptidyl peptidase- 4: a possible therapeutic strategy.
Marziye Poornabi,¹ Sanam Rezazadeh,² Mahsa Saeidi,³ Solmaz Abolhasanzade,⁴ Fatemeh Akbarian,^5,*
1. Genetics Department, Ale-Taha institute of Higher Education
2. Genetics Department, Ale-Taha institute of Higher Education
3. Genetics Department, Ale-Taha institute of Higher Education
4. Genetics Department, Ale-Taha institute of Higher Education
5. Genetics Department, Ale-Taha institute of Higher Education
Introduction: Coronavirus disease 2019 (COVID-19) is a severe global pandemic and a new form of coronavirus, named SARS-CoV-2. Although it has many common symptoms such as tiredness, dry cough and fever, this illness appears to perform differently in many ways and symptoms form a person to others. Recent reports express that elder sufferers with previous illness, like diabetes, were at superior danger for mortality and COVID-19. One of the risk factors for SARS-CoV-2 infection in sufferers with diabetes is high blood glucose stage due to hyperglycemic hormones.
Methods: Dipeptidyl peptidase- 4 (DPP-4) also named as adenosine deaminase binding protein or CD26, is a major protein implicated for the action of a catalyst by enzymatic activity and binder for proteins and ligands. It exists both on the cell membrane and soluble in plasma and is expressed in epithelial and endothelial cells, such as blood vessels, mucosal glands, pancreas and T cells.
Results: DPP-4 directly influences glucose levels and homeostasis, which increases the development of metabolic diseases. DPP-4 is also in charge of decreasing insulin secretion and metabolism of adipose tissue by degradation of incretins, such as glucagon like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptides. These processes happen when food containing glucose is consumed. Furthermore, DPP-4 is associated with many immunological functions, such as modulating NF-kB pathway, upregulating CD86 statement, and immunological control by activating T cells. DPP-4 can advance inflammation in sufferers with type 2 diabetes, by regulating non- catalytic and catalytic metabolism. Thus, DPP4 inhibition has an impact on all these affected pathways in the immune system. DPP-4 inhibitors prevent the reduction of the incretins, which helps lower the blood glucose level. Interestingly, a study indicated that sufferers with diabetes and COVID-19 who are subscribed with DPP-4 inhibitors, express 64% less strict COVID-19. On the other hand, T cells play an important role in antiviral response, leading to cytokine storm. Based on studies, DPP-4/ CD26 have important function on T cells. It is predicted that DPP-4/ CD26 can interact with SARS-CoV-2 spike glycoproteins and this is a possible way for the virus to enter the cell and can infect the cell. The activation of T cells increases expression of CD26. The construction of TH1-type cytokines like interferon-gamma and CD26+ CD4+ T cells help differentiation of B cells into antibody-producing plasma cells. In addition, high expression of CD26 could have an influence on the migration of T cells. CD26+ T cells generate IL-2 by the interaction of CD26 and CD3 on T cells with plate-bound monoclonal antibodies (mAbs). Thus, using DPP-4 inhibitors is a therapeutic way that can bind to DPP-4/CD26 and suppress all these pathways that could decrease risk of cytokine storm in COVID-19.
Conclusion: In conclusion, targeting DPP-4 receptors especially expressed on T-cells, have anti-inflammatory roles, helping improvement of sufferers with diabetes and COVID-19. Furthermore, it can be useful in decreasing the danger of severe COVID-19 in patients without diabetes. Based on this review, we suggest more investigation on CD26 immunotherapy, possibly as an appropriate treatment strategy for COVID-19.
Keywords: COVID-19; Dipeptidyl peptidase 4; CD26; DPP4 inhibitor; Diabetes