PMID- 22787171
OWN - NLM
STAT- MEDLINE
DCOM- 20130417
LR  - 20211021
IS  - 1935-5548 (Electronic)
IS  - 0149-5992 (Print)
IS  - 0149-5992 (Linking)
VI  - 35
IP  - 11
DP  - 2012 Nov
TI  - Altered phenotype of peripheral blood dendritic cells in pediatric type 1 
      diabetes.
PG  - 2303-10
LID - 10.2337/dc11-2460 [doi]
AB  - 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/muL, P = 0.009, n = 31) and 
      plasmacytoid DCs (pDCs) (9.47 vs. 14.6 cells/muL, 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-kappaB pathway (P = 0.063, n = 39) was seen in 
      mDCs from children with beta-cell autoantibodies, which is possibly related to the 
      reduced CCR2 expression, since CCR2 on mDCs was downregulated by nuclear 
      factor-kappaB-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.
FAU - Nieminen, Janne K
AU  - Nieminen JK
AD  - Immune Response Unit, Department of Vaccination and Immune Protection, National 
      Institute for Health and Welfare, Helsinki, Finland. janne.nieminen@thl.fi
FAU - Vakkila, Jukka
AU  - Vakkila J
FAU - Salo, Harri M
AU  - Salo HM
FAU - Ekstrom, Nina
AU  - Ekstrom N
FAU - Harkonen, Taina
AU  - Harkonen T
FAU - Ilonen, Jorma
AU  - Ilonen J
FAU - Knip, Mikael
AU  - Knip M
FAU - Vaarala, Outi
AU  - Vaarala O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120711
PL  - United States
TA  - Diabetes Care
JT  - Diabetes care
JID - 7805975
SB  - IM
MH  - Chemotaxis/genetics/physiology
MH  - Child
MH  - Child, Preschool
MH  - Dendritic Cells/*cytology/*immunology/metabolism
MH  - Diabetes Mellitus, Type 1/genetics/*immunology
MH  - Female
MH  - Humans
MH  - Male
MH  - Myeloid Cells/cytology/immunology/metabolism
MH  - Real-Time Polymerase Chain Reaction
PMC - PMC3476907
EDAT- 2012/07/13 06:00
MHDA- 2013/04/18 06:00
PMCR- 2013/11/01
CRDT- 2012/07/13 06:00
PHST- 2012/07/13 06:00 [entrez]
PHST- 2012/07/13 06:00 [pubmed]
PHST- 2013/04/18 06:00 [medline]
PHST- 2013/11/01 00:00 [pmc-release]
AID - dc11-2460 [pii]
AID - 2460 [pii]
AID - 10.2337/dc11-2460 [doi]
PST - ppublish
SO  - Diabetes Care. 2012 Nov;35(11):2303-10. doi: 10.2337/dc11-2460. Epub 2012 Jul 11.