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Updated: Dec 28, 2025

Generation of a Mouse Spontaneous Autoimmune Thyroiditis Model
Published on: March 17, 2023
Decreased shedding dipeptidyl peptidase 4 from membrane in Hashimoto's thyroiditis
Wenjie Xu1, Yongping Liu1, Xuebing Cheng1
1Department of Endocrinology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261031, China.
Aims:
This study aimed to determine the concentration and enzymatic activity of dipeptidyl peptidase 4 (DPP4) in serum and peripheral blood mononuclear cells (PBMCs) from patients with Hashimoto's thyroiditis (HT) and to explore the potential mechanism of the abnormal DPP4 in HT development.
Methods:
A total of 33 newly diagnosed HT patients and 31 age- and sex-matched healthy controls were enrolled. Clinical characteristics and thyroid function data were collected for all participants. Serum DPP4 and kallikrein-related peptidase 5 (KLK5) concentrations were measured by sandwich enzyme-linked immunosorbent assay. DPP4 enzymatic activities in serum and PBMCs were determined by enzymatic assay. DPP4, KLK5 and interferon (IFN)-γ mRNA expression levels in PBMCs were evaluated by quantitative real-time polymerase chain reaction.
Results:
Serum DPP4 level and activity were significantly lower in the HT group compared with the control group. However, DPP4 mRNA expression was significantly increased and both serum KLK5 concentration and KLK5 mRNA expression in PBMCs were significantly decreased in HT patients. Correlation analyses revealed that DPP4 concentration was positively correlated with DPP4 enzymatic activity in serum. No significant difference in DPP4 activity was found in PBMCs. DPP4 enzymatic activity in PBMCs was negatively correlated with DPP4 enzymatic activity in serum. IFN-γ mRNA expression in PBMCs was significantly increased in HT patients.
Conclusions:
DPP4 is involved in the development and pathological process of HT. Decreased cleavage of membrane-anchored DPP4 by KLK5 may be responsible for the decreased serum DPP4 levels in HT patients.
Insights
Serum dipeptidyl peptidase 4 (DPP4) levels and activity are lower in Hashimoto
Area of Science:
- Endocrinology
- Immunology
- Biochemistry
Background:
- Hashimoto's thyroiditis (HT) is an autoimmune disease affecting the thyroid gland.
- Dipeptidyl peptidase 4 (DPP4) is an enzyme with known roles in immune regulation.
- Understanding DPP4's role in HT may reveal new therapeutic targets.
Purpose of the Study:
- To quantify DPP4 concentration and enzymatic activity in serum and peripheral blood mononuclear cells (PBMCs) of HT patients.
- To investigate the relationship between DPP4 and other factors in HT pathogenesis.
- To explore the potential mechanism behind altered DPP4 in HT.
Main Methods:
- Enrolled 33 newly diagnosed HT patients and 31 healthy controls.
- Measured serum DPP4 and kallikrein-related peptidase 5 (KLK5) using ELISA.
- Assessed DPP4 enzymatic activity and mRNA expression in serum and PBMCs.
- Evaluated KLK5 and interferon-gamma (IFN-γ) mRNA expression in PBMCs via qPCR.
Main Results:
- HT patients showed significantly lower serum DPP4 levels and activity compared to controls.
- DPP4 mRNA expression was elevated in HT patients' PBMCs.
- Serum KLK5 concentration and KLK5 mRNA expression in PBMCs were significantly reduced in HT patients.
- IFN-γ mRNA expression in PBMCs was significantly increased in HT patients.
Conclusions:
- DPP4 plays a role in the development and pathology of Hashimoto's thyroiditis.
- Reduced cleavage of membrane-bound DPP4 by KLK5 may contribute to lower serum DPP4 levels in HT.
- Altered DPP4 and KLK5 levels suggest a complex interplay in HT pathogenesis.
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