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Altered phenotype of peripheral blood dendritic cells in pediatric type 1 diabetes.
Nieminen, Janne K; Vakkila, Jukka; Salo, Harri M; Ekström, Nina; Härkönen, Taina; Ilonen, Jorma; Knip, Mikael; Vaarala, Outi.
Afiliação
  • Nieminen JK; Immune Response Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland. janne.nieminen@thl.fi
Diabetes Care ; 35(11): 2303-10, 2012 Nov.
Article em En | MEDLINE | ID: mdl-22787171
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 ß-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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Dendríticas / Diabetes Mellitus Tipo 1 Limite: Child / Child, preschool / Female / Humans / Male Idioma: En Ano de publicação: 2012 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Dendríticas / Diabetes Mellitus Tipo 1 Limite: Child / Child, preschool / Female / Humans / Male Idioma: En Ano de publicação: 2012 Tipo de documento: Article