Cut to the chase: a review of CD26/dipeptidyl peptidase-4's (DPP4) entanglement in the immune system

Klemann C, Wagner L, Stephan M, von Hörsten S (2016)

Publication Type: Journal article, Review article

Publication year: 2016

Journal

Clinical and Experimental Immunology Wiley-Blackwell

Book Volume: 185

Pages Range: 1-21

Journal Issue: 1

DOI: 10.1111/cei.12781

Abstract

CD26/DPP4 (dipeptidyl peptidase 4/DP4/DPPIV) is a surface T cell activation antigen and has been shown to have DPP4 enzymatic activity, cleaving-off amino-terminal dipeptides with either L-proline or L-alanine at the penultimate position. It plays a major role in glucose metabolism by N-terminal truncation and inactivation of the incretins glucagon-like peptide-1 (GLP) and gastric inhibitory protein (GIP). In 2006, DPP4 inhibitors have been introduced to clinics and have been demonstrated to efficiently enhance the endogenous insulin secretion via prolongation of the half-life of GLP-1 and GIP in patients. However, a large number of studies demonstrate clearly that CD26/DPP4 also plays an integral role in the immune system, particularly in T cell activation. Therefore, inhibition of DPP4 might represent a double-edged sword. Apart from the metabolic benefit, the associated immunological effects of long term DPP4 inhibition on regulatory processes such as T cell homeostasis, maturation and activation are not understood fully at this stage. The current data point to an important role for CD26/DPP4 in maintaining lymphocyte composition and function, T cell activation and co-stimulation, memory T cell generation and thymic emigration patterns during immune-senescence. In rodents, critical immune changes occur at baseline levels as well as after in-vitro and in-vivo challenge. In patients receiving DPP4 inhibitors, evidence of immunological side effects also became apparent. The scope of this review is to recapitulate the role of CD26/DPP4 in the immune system regarding its pharmacological inhibition and T cell-dependent immune regulation.

Authors with CRIS profile

Stephan von Hörsten Professur für Experimentelle Biomedizin

Involved external institutions

Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) DSAKU (Deutschsprachige Selbsthilfegruppe für Alkaptonurie e.V.) DE Germany (DE)

How to cite

APA:

Klemann, C., Wagner, L., Stephan, M., & von Hörsten, S. (2016). Cut to the chase: a review of CD26/dipeptidyl peptidase-4's (DPP4) entanglement in the immune system. Clinical and Experimental Immunology, 185(1), 1-21. https://dx.doi.org/10.1111/cei.12781

MLA:

Klemann, Christian, et al. "Cut to the chase: a review of CD26/dipeptidyl peptidase-4's (DPP4) entanglement in the immune system." Clinical and Experimental Immunology 185.1 (2016): 1-21.

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