Triggering endogenous immunosuppressive mechanisms by combined targeting of Dipeptidyl peptidase IV (DPIV/CD26) and Aminopeptidase N (APN/ CD13) — A novel approach for the treatment of inflammatory bowel disease

Bank, Ute; Heimburg, Anke; Helmuth, Martin; Stefin, Sofia; Lendeckel, Uwe; Reinhold, Dirk; Faust, Jürgen; Fuchs, Petra; Sens, Bianca; Neubert, Klaus; Täger, Michael; Ansorge, Siegfried

doi:10.1016/j.intimp.2006.09.014

Cited by 47 publications

(37 citation statements)

References 48 publications

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“…The expanding list of autoimmune diseases in which anti-CD13 autoantibodies and/or high levels of aminopeptidase activity are present [29,81,82] suggests their participation in the pathogenesis of these diseases. IBD and rheumatoid arthritis, for instance, could be interesting models in which to test the efficacy of anti-CD13 targeting tools, especially in view of the recent reports on antiinflammatory effects of combined CD13/CD26 blockade in vivo [9,83].…”

Section: Discussionmentioning

confidence: 99%

The moonlighting enzyme CD13: old and new functions to target

Mina‐Osorio

2008

Trends in Molecular Medicine

334

369

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Aminopeptidase N (CD13) is a widely expressed ectoenzyme with functions that do not always depend on its enzymatic activity: an aspect that has been overlooked. Numerous CD13-targeting tools have been developed in the last few years. Several of them are already undergoing clinical trials, and there are promising reports on the effectiveness of others in animal models of disease. However, their efficacy might be obscured by their effects on unrecognized functions of CD13, resulting in unexpected complications. The purpose of this review is (i) to discuss the various functions ascribed to CD13 and the possible mechanisms behind them and (ii) to consider some of the questions that need to be answered to achieve a better understanding of the biological relevance of these functions, a more precise interpretation of the results obtained after their manipulation and a more rational design of CD13-targeting agents.

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Section: Discussionmentioning

confidence: 99%

The moonlighting enzyme CD13: old and new functions to target

Mina‐Osorio

2008

Trends in Molecular Medicine

334

369

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“…4) However, the effect of DPPIV inhibition on IBDs has been controversial. There is a report showing that the administration of a DPPIV inhibitor alone failed to ameliorate experimental colitis, 5) indicating the difficulty of determining an appropriate dose and timecourse for the administration required to suppress tissue DPPIV activities. DPPIV may have diverse effects on the pathogenesis of IBD.…”

mentioning

confidence: 99%

Contribution of Dipeptidyl Peptidase IV to the Severity of Dextran Sulfate Sodium-Induced Colitis in the Early Phase

Iwaya

Fujii

Hagio

et al. 2013

Bioscience, Biotechnology, and Biochemistry

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“…Inhibiting DPP‐4 and APN enhances TGF‐ β secretion, which suggests the potential therapeutic role of DPP‐4 inhibitors on the treatment of MS and other autoimmune diseases . Inhibition of DPP‐4 and APN improves inflammatory bowel disease in mouse models by up‐regulating TGF‐ β and initiating endogenous immunosuppression . DPP‐4 inhibitors can also stimulate pokeweed mitogen‐stimulated peripheral blood mononuclear cells and T cell to secrete TGF‐ β , whereas anti‐TGF‐ β antibodies block this effect, which suggests that TGF‐ β plays a key role in the effect of DPP‐4 inhibition on cytokine production .…”

Section: Effect Of Dpp‐4/cd26 and Its Inhibitors On The Immune Systemmentioning

confidence: 99%

The New insights from DPP‐4 inhibitors: their potential immune modulatory function in autoimmune diabetes

Zhao

Yang

Wang

et al. 2014

Diabetes Metabolism Res

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Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of anti-diabetic agents that are widely used in clinical practice to improve glycemic control and protect β-cell function in patients with type 2 diabetes. DPP-4 is also known as lymphocyte cell surface protein CD26 and plays an important role in T-cell immunity. Autoimmune diabetes, a T-cell mediated organ-specific disease, is initiated by the imbalance between pathogenic and regulatory T-lymphocytes. DPP-4 inhibitors can suppress pathogenic effects of Th1 and Th17 cells and up-regulate Th2 cells and regulatory T cells, which play a critical role in ameliorating autoimmune diabetes. This provides a basis for the potential use of DPP-4 inhibitors in the treatment of autoimmune diabetes. Recent studies suggest that DPP-4 inhibitors improve β-cell function and attenuate autoimmunity in type 1 diabetic mouse models. However, there are few clinical studies on the treatment of autoimmune diabetes with DPP-4 inhibitors. Further studies are warranted to confirm the therapeutic effects of DPP-4 inhibitors on autoimmune diabetes in humans.

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Triggering endogenous immunosuppressive mechanisms by combined targeting of Dipeptidyl peptidase IV (DPIV/CD26) and Aminopeptidase N (APN/ CD13) — A novel approach for the treatment of inflammatory bowel disease

Cited by 47 publications

References 48 publications

The moonlighting enzyme CD13: old and new functions to target

The moonlighting enzyme CD13: old and new functions to target

Contribution of Dipeptidyl Peptidase IV to the Severity of Dextran Sulfate Sodium-Induced Colitis in the Early Phase

The New insights from DPP‐4 inhibitors: their potential immune modulatory function in autoimmune diabetes

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