Altered phenotype of peripheral blood dendritic cells in pediatric type 1 diabetes.
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.


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.
Immune Response Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland. janne.nieminen@thl.fi
Janne K
JK
Nieminen
Jukka
J
Vakkila
Harri M
HM
Salo
Nina
N
Ekström
Taina
T
Härkönen
Jorma
J
Ilonen
Mikael
M
Knip
Outi
O
Vaarala
D002633:Chemotaxis / Q000235:genetics / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction