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- Gogolak, P, et al.
(författare)
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Differentiation of CD1a- and CD1a+ monocyte-derived dendritic cells is biased by lipid environment and PPARgamma
- 2007
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 109:2, s. 643-652
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Tidskriftsartikel (refereegranskat)abstract
- Accumulating data have shown that the microenvironment of dendritic cells modulates subtype differentiation and CD1 expression, but the mechanisms by which exogenous factors confer these effects are poorly understood. Here we describe the dependence of CD1a− monocyte-derived dendritic cell (moDC) development on lipids associated with the expression of peroxisome proliferator-activated receptor–gamma (PPARγ). We also show the consecutive differentiation of immature CD1a−PPARγ+ moDCs to CD1a+PPARγ− cells limited by serum lipoproteins and terminated by proinflammatory cytokines. Immature CD1a− moDCs possess higher internalizing capacity than CD1a+ cells, whereas both activated subtypes have similar migratory potential but differ in their cytokine and chemokine profiles, which translates to distinct T-lymphocyte–polarizing capacities. CD1a+ moDCs stand out by their capability to secrete high amounts of IL-12p70 and CCL1. As lipoproteins skew moDC differentiation toward the generation of CD1a−PPARγ+ cells and inhibit the development of CD1a+PPARγ− cells, we suggest that the uptake of lipids results in endogenous PPARγ agonists that induce a cascade of gene transcription coordinating lipid metabolism, the expression of lipid-presenting CD1 molecules, subtype dichotomy, and function. The presence of CD1a−PPARγ+ and CD1a+PPARγ− DCs in lymph nodes and in pulmonary Langerhans cell histiocytosis confirms the functional relevance of these DC subsets in vivo.
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- Rethi, B, et al.
(författare)
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SLAM/SLAM interactions inhibit CD40-induced production of inflammatory cytokines in monocyte-derived dendritic cells
- 2006
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 107:7, s. 2821-2829
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Tidskriftsartikel (refereegranskat)abstract
- Signaling lymphocyte activation molecule (SLAM, CD150, or SLAMF1) is a self-ligand receptor on the surface of activated T- and B-lymphocytes, macrophages, and dendritic cells (DCs). Here we examine the effect of SLAM/SLAM interactions on CD40L-induced CD40 signaling pathways in human DCs. CD40L-expressing L929 cells induced DCs to produce interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-12, which was strongly inhibited by coexpression of SLAM on the surface of the L929 cells. Similarly, transfection of DCs with SLAM strongly reduced CD40L-induced IL-12 production. Furthermore, the negative effect of SLAM/SLAM interactions on CD40L-induced DC activation was also detected in the presence of lipopolysaccharide (LPS). LPS-induced IL-12 secretion, however, was not inhibited by SLAM engagement. CD40L-activated DCs affected by exposure to SLAM/SLAM engagement were impaired in their ability to induce differentiation of naive T lymphocytes into interferon-γ (IFN-γ)–producing T-helper 1 (Th1) effector cells. These inhibitory effects were not the result of a general unresponsiveness of DCs to CD40L, as SLAM/SLAM interactions did not prevent CD40L-induced up-regulation of CD83, CD86, or human leukocyte antigen (HLA)–DQ on the surface of DCs. Taken together, the results indicate that SLAM/SLAM interactions inhibit CD40-induced signal transduction in monocyte-derived dendritic cells, an effect that was not detectable in earlier studies using anti-SLAM monoclonal antibodies.
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