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

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• 作者：Andrá ; s Zó ; ka^a ; Gá ; bor Barna^b ; Orsolya Hadarits^c ; Zahra Al-Aissa^a ; Barna Wichmann^d ; Gyö ; rgyi M疟zes^a ; Anikó ; Somogyi^a ; Gá ; bor Firneisz^a ; ^{firneisz.gabor@med.semmelweis-univ.hu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：BAL ; bronchoalveolar lavage ; CCL ; chemokine (C-C motif) ligand ; CNTRL ; control ; CST ; Chi-square test ; CTLA-4 ; cytotoxic T-lymphocyte-associated protein 4 ; CXCL ; chemokine (C-X-C motif) ligand ; CXCR3 ; C-X-C chemokine receptor type 3 ; DPP4 ; dipeptidyl peptidase-4 ; ELISA ; enzyme-linked immunosorbent assay ; Foxp3 ; forkhead box P3 ; GADA ; glutamic acid decarboxylase autoantibody ; GLP1 ; glucagon-like peptide 1 ; GLP1R ; GLP1 receptor ; ICA ; islet cell autoantibody ; IL ; interleukin ; HbA1C ; glycated hemoglo
• 刊名：Human Immunology
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：76
• 期：9
• 页码：667-672
• 全文大小：904 K

文摘

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_regs 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 GLP1^7–36 concentrations were determined. GLP1^9–36 concentrations were calculated. CXCR3 expression (flow cytometry) was higher on the CD25^−/lowFoxp3⁺ than on the CD25⁺Foxp3⁺ T_regs independently from T1DM, suggesting that CD25^−/lowFoxp3⁺ T_regs 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.