Dipeptidylpeptidase IV (DPIV) and Alanyl-Aminopeptidases (AAPs) as a New Target Complex for Treatment of Autoimmune and Inflammatory Diseases—Proof of Concept in a Mouse Model of Colitis
In summary these results strongly support the idea that AAPs and DPIV represent a promising target complex for the pharmacological therapy of T cell-mediated diseases by preserving and enhancing endogenous immunosuppressive mechanisms. Whereas inhibitors of AAPs appear to preferentially act on CD4+CD25+ regulatory T cells by preserving their immunosuppressive activity via enhanced expression of immunosuppressive cytokines and FOXP3, inhibition of DPIV leads to increased production/release of TGF-β1 and inhibition of cellular proliferation of predominantly activated effector T cells. Thus, specific inhibition of DPIV and AAPs via small molecular compounds provides a new approach for the pharmacological treatment of autoimmune and inflammatory diseases that simultaneously interferes with two major axis of T cell function.
KeywordsDextran Sulphate Sodium Suppressive Activity FOXP3 Expression Immunosuppressive Cytokine Target Complex
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