Altered crosstalk in the dipeptidyl peptidase-4-incretin-immune system in type 1 diabetes: A hypothesis generating pilot study

Abstract

Both GLP17–36 (via GLP1 receptor) and the dipeptidyl peptidase-4 (DPP4) cleaved form of GLP1 (GLP19–36, independently of GLP1R) may modulate the response of lymphocytes to cytokine stimuli. The incretin axis, CXCR3 (receptor of DPP4 ligand cytokines CXCL9–11) expression on Tregs and hematologic parameters were assessed in 34 patients with long standing type 1 diabetes (T1DM) and in 35 healthy controls. Serum DPP4 (sDPP4) activity, plasma total GLP1 and GLP17–36 concentrations were determined. GLP19–36 concentrations were calculated. CXCR3 expression (flow cytometry) was higher on the CD25−/lowFoxp3+ than on the CD25+Foxp3+ Tregs independently from T1DM, suggesting that CD25−/lowFoxp3+ Tregs are possibly waiting for orientational chemotactic stimuli in a “standby mode”. The higher sDPP4 activities in T1DM were inversely correlated with GLP17–36 levels and GLP19–36 levels directly with lymphocyte counts in controls. Our results might indicate an altered DPP4-incretin system and altered immunoregulation including a potentially dysfunctional GLP19–36 signaling in T1DM.