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

Abstract

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.

Th17 Cells in Cancer: The Ultimate Identity Crisis

“…In contrast to Th17 cells, Treg cells express low levels of CD26 and high levels of the ectonucleotidases CD39 and CD73 (32). Moreover, CD26 up-regulation correlates with disease activity in human autoimmune manifestations linked to the presence of pathogenic Th17 cells, such as rheumatoid arthritis (31) and diabetes (33). Elevated CD26 expression – as well as high expression of the inducible costimulator (ICOS), the IL-23 receptor (IL-23R), and chemokine receptor 6 (CCR6) – distinguishes Th17 cells from other human T cell subsets (34, 35).…”

Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins

“…While DPP4 inhibition was shown to suppress the development of Th17 cell differentiation, knock-down of DPP2 in resting T cells of mutant mice led to differentiation into IL-17-releasing Th17 cells [48,125,126]. In fact, inhibition of DPP4 has been proposed for the treatment of the autoimmune disease diabetes type 1 by suppressing the pathogenic effects of Th1 and Th17 cells and up-regulating Th2 cells [127]. DPP2 selective inhibitor AX8819 was designed for a prognostic marker of B cell chronic leucocytic leukaemia, as well as a potential drug target to induce apoptosis in malignant B cells [126].…”

The effect of dipeptidyl peptidase-IV inhibition on circulating T cell subpopulations in patients with type 2 diabetes mellitus

“…On the other hand, DPP-IV inhibitors were surprisingly described to increase the levels of TGF-beta possibly participating on the decrease of the CD3+ cell effector functions in a mouse model of experimental autoimmune encephalomyelitis [27]. A similar immunosuppressive mechanism might participate on the DPP-IV inhibition-induced decrease of graft rejection [31] as well as on the proposed preservation of beta cell mass in patients with autoimmune type 1 diabetes [32]. depend on the actual composition of the given microenvironment [34,35].…”