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Altered phenotype of peripheral blood dendritic cells in pediatric type 1 diabetes
Janne K Nieminen1, Jukka Vakkila, Harri M Salo
1Immune Response Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland. janne.nieminen@thl.fi
Insights
Type 1 diabetes (T1D) is associated with fewer dendritic cells (DCs) and reduced expression of CC chemokine receptor 2 (CCR2) on these cells. This may impact immune responses in T1D.
Area of Science:
- Immunology
- Endocrinology
- Cell Biology
Background:
- Dendritic cells (DCs) are crucial for T-cell activation and regulation.
- Altered numbers of blood DCs have been observed in type 1 diabetes (T1D).
Purpose of the Study:
- To characterize the phenotypic properties of DCs in children with T1D.
- To investigate the expression of CC chemokine receptor 2 (CCR2) on DCs in T1D.
Main Methods:
- Case-control study involving 90 children.
- Flow cytometry and quantitative real-time PCR (qPCR) were used to analyze DC numbers and marker expression.
- Analysis included myeloid DCs (mDCs) and plasmacytoid DCs (pDCs).
Main Results:
- Decreased numbers of mDCs and pDCs were found in children with recent-onset T1D.
- Reduced expression of CCR2 was observed on both mDCs and pDCs from T1D patients.
- qPCR confirmed reduced CCR2 expression in isolated mDCs.
- A trend towards enhanced nuclear factor-κB pathway responsiveness was noted in mDCs from children with beta-cell autoantibodies.
Conclusions:
- The findings suggest a functionally significant DC abnormality in T1D.
- Reduced CCR2 expression on DCs may affect immune cell trafficking and T-cell differentiation.
- This abnormality could impact the initiation and quality of immune responses in T1D.
Objective:
Dendritic cells (DCs) are largely responsible for the activation and fine-tuning of T-cell responses. Altered numbers of blood DCs have been reported in type 1 diabetes (T1D). We aimed at characterizing the less well-known phenotypic properties of DCs in T1D.
Research Design And Methods:
In a case-control setting, samples from a total of 90 children were studied by flow cytometry or by quantitative real-time PCR (qPCR).
Results:
We found decreased numbers of myeloid DCs (mDCs) (8.97 vs. 13.4 cells/μL, P = 0.009, n = 31) and plasmacytoid DCs (pDCs) (9.47 vs. 14.6 cells/μL, P = 0.018, n = 30) in recent-onset T1D. Using a panel of antibodies against functionally important DC markers, we detected a decreased expression of CC chemokine receptor 2 (CCR2) on mDCs (percentage above negative control, P = 0.002, n = 29) and pDCs (median intensity, P = 0.003, n = 30) from T1D patients. In an independent series of children, the reduced expression of CCR2 was confirmed by qPCR in isolated mDCs (P = 0.043, n = 20). Serum concentrations of CCR2 ligands monocyte chemotactic protein-1 and -3 did not differ between the groups. A trend for an enhanced responsiveness of the nuclear factor-κB pathway (P = 0.063, n = 39) was seen in mDCs from children with β-cell autoantibodies, which is possibly related to the reduced CCR2 expression, since CCR2 on mDCs was downregulated by nuclear factor-κB-activating agents.
Conclusions:
Given the role of CCR2 in DC chemotaxis and in DC-elicited Th1 differentiation, our results may indicate a functionally important DC abnormality in T1D affecting the initiation and quality of immune responses.
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