title: Cut to the chase: a review of CD26/dipeptidyl peptidase-4's (DPP4) entanglement in the immune system.
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.affiliation: Center of Pediatric Surgery, Hannover Medical School, Hannover.|Center of Chronic Immunodeficiency, University Medical Center Freiburg, University Medical Center Freiburg.
authors.forename: C
authors.initials: C
authors.lastname: Klemann
authors.affiliation: Deutschsprachige Selbsthilfegruppe für Alkaptonurie (DSAKU) e.V.|Department for Experimental Therapy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Wagner
authors.affiliation: Clinic for Psychosomatics and Psychotherapy, Hannover Medical School, Hannover.
authors.forename: M
authors.initials: M
authors.lastname: Stephan
authors.affiliation: Department for Experimental Therapy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: von Hörsten
mesh_terms: D000818:Animals; D002465:Cell Movement; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000276:immunology*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D005786:Gene Expression Regulation; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000276:immunology; D005947:Glucose / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007156:Immunologic Memory; D007328:Insulin / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000473:pathology
chemical_list: D018925:Chemokines; D016207:Cytokines; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007328:Insulin; C085114:granulocyte inhibitory protein, human; D052216:Glucagon-Like Peptide 1; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D005947:Glucose
keywords: B cell; T cells; autoimmunity; cell activation; chemokines