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Review
. 2021 Jun:188:114517.
doi: 10.1016/j.bcp.2021.114517. Epub 2021 Mar 13.

Dipeptidyl peptidase 4 inhibitors: Applications in innate immunity?

R Yazbeck  1 , S E Jaenisch  2 , C A Abbott  3
Affiliations
Review

Dipeptidyl peptidase 4 inhibitors: Applications in innate immunity?

R Yazbeck et al. Biochem Pharmacol. 2021 Jun.

Abstract

Dipeptidyl peptidase (DPP)-4 inhibitors are a class of orally available, small molecule inhibitors that prolong the insulinotropic activity of the incretin hormone glucagon-like peptide-1 (GLP-1) and are highly effective for the treatment of Type-2 diabetes. DPP4 can also cleave several immunoregulatory peptides including chemokines. Emerging evidence continues to implicate DPP4 inhibitors as immunomodulators, with recent findings suggesting DPP4 inhibitors modify specific aspects of innate immunity. This review summarises recent insights into how DPP4 inhibitors could be implicated in endothelial, neutrophil and monocyte/macrophage mediated immunity. Additionally, this review highlights additional avenues of research with DPP4 inhibitors in the context of the COVID-19 pandemic.

Keywords: DPP4 inhibitor; Dipeptidyl peptidase; Immunity; Innate immunity; Macrophage; Neutrophil; Sitagliptin.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

None
Graphical abstract
Fig. 1
Fig. 1
Summary of main health conditions discussed in this review and the described physiological and molecular effects of DPP4 inhibition. ↓ indicates decreased expression and ↑ indicates increased expression. Image created with BioRender.com.
Fig. 2
Fig. 2
Proposed model for role of DPP4 inhibitors in modulating innate immune responses. DPP4 cleaves several immunoregulatory peptides with demonstrated roles in stimulating release of chemotactic factors, promoting tethering and migration of innate immune cells and stimulate innate immune cell activity, including secretion of reactive oxygen species and phagocytic activity. DPP4 inhibitors could block the proteolytic cleavage of these regulatory factors, leading to downstream anti-inflammatory effects.
See this image and copyright information in PMC

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