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Published on: May 6, 2013
Role of immune dysfunction in pathogenesis of type 1 diabetes mellitus in children
Jin-Shui He1, Pu-Song Xie1, Dao-Shu Luo2
1Department of Pediatrics, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, China.
Insights
Children with type 1 diabetes mellitus (T1DM) exhibit immune dysfunction, characterized by increased inflammatory cytokines and chemokines, and decreased regulatory T cells (Tregs). This immune imbalance is crucial in T1DM development.
Area of Science:
- Immunology
- Endocrinology
- Pediatrics
Background:
- Type 1 diabetes mellitus (T1DM) is an autoimmune disease with complex pathogenesis.
- Cytokines, chemokines, and regulatory T cells (Tregs) are key immune mediators implicated in T1DM.
Purpose of the Study:
- To investigate the roles of specific cytokines, chemokines, and Tregs in pediatric T1DM pathogenesis.
- To compare immune profiles between children with T1DM and healthy controls.
Main Methods:
- Serum cytokine and chemokine levels were measured using ELISA in 35 children with T1DM and 30 controls.
- Peripheral blood mononuclear cells (PBMCs) were stimulated, and cytokine secretion was analyzed.
- Flow cytometry quantified the percentage of CD4(+)CD25(+)Foxp3(+) Tregs in PBMCs.
Main Results:
- Children with T1DM showed significantly elevated serum IL-1α, IL-6, TNF-α, and MIP-1α compared to controls.
- Stimulated PBMCs from T1DM patients secreted more IL-1α and TNF-α, but less IL-10.
- The proportion of Tregs was significantly lower in children with T1DM.
Conclusions:
- Immune dysfunction, marked by elevated pro-inflammatory cytokines (IL-1α, IL-6, TNF-α, MIP-1α), reduced IL-10, and decreased Tregs, is central to pediatric T1DM pathogenesis.
- These findings highlight potential therapeutic targets for T1DM.
Objectives:
To investigate the function of cytokines, chemokines, and regulatory T cells (Tregs) in the pathogenesis of type 1 diabetes mellitus (T1DM) in children.
Methods:
A total of 35 children with T1DM and 30 healthy controls were enrolled in this study. Levels of serum cytokines (IL-1α, IL-6, IL-10, IL-12, and TNF-α) and chemokines (MIP-1α, MIP-1α and MCP-1) were detected by enzyme-linked immunosorbent assay. Peripheral blood mononuclear cells (PBMCs) were isolated and culture supernatant of phytohaemagglutinin (PHA)-stimulated PBMCs was subjected to ELISA for levels of cytokines (IL-1α, IL-6, IL-10, IL-12 and TNF-α) in T1DM and control group. Furthermore, flow cytometry was used to determine the percentage of Tregs in PBMCs of two groups.
Results:
Levels of serum cytokines including IL-1α, IL-6, IL-10 and TNF-α as well as chemokines, such as MIP-1α and MIP-1α in children with T1DM children were significantly higher than those in healthy controls (P<0.05, respectively). PBMCs with PHA stimulation in T1DM group secreted more IL-1α and TNF-α (P<0.05, respectively), but less IL-10 (P<0.05), as compared with control group. Furthermore, the proportion of CD4(+), CD25(+), Foxp3(+), Tregs in PBMCs isolated from children with T1DM was obviously lower than those in healthy controls (P<0.05).
Conclusions:
Immune dysfunction, with upregulation of inflammatory factors such as IL-1α, IL-6, TNF-α and MIP-1α, downregulation of IL-10 and Tregs, plays an important role in the pathogenesis of T1DM in children.
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