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

摘要

Both GLP1(7-36) (via GLP1 receptor) and the dipeptidyl peptidase-4 (DPP4) cleaved form of GLP1 (GLP1(9-36), 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 T(reg)s and hematologic parameters were assessed in 34 patients with long standing type I diabetes (T1DM) and in 35 healthy controls. Serum DPP4 (sDPP4) activity, plasma total GLP1 and GLP1(7-36) concentrations were determined. GLP1(9-36) concentrations were calculated. CXCR3 expression (flow cytometry) was higher on the CD25(-/low)Foxp3(+) than on the CD25(+)Foxp3(+) T(reg)s independently from T1DM, suggesting that CD25(-/low)Foxp3(+) T(reg)s are possibly waiting for orientational chemotactic stimuli in a "standby mode". The higher sDPP4 activities in T1DM were inversely correlated with GLP1(7-36) levels and GLP1(9-36) levels directly with lymphocyte counts in controls. Our results might indicate an altered DPP4-incretin system and altered immunoregulation including a potentially dysfunctional GLP1(9-36) signaling in T1DM. (C) 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.