Glucocorticoids hamper the<i>ex vivo</i>maturation of lung dendritic cells from their low autofluorescent precursors in the human bronchoalveolar lavage: decreases in allostimulatory capacity and expression of CD80 and CD86

Verhoeven, Gert T.; Haarst, J. M. W. Van; Wit, Harm J. de; Simons, Peter J.; Hoogsteden, H. C.; Drexhage, H. A.

doi:10.1046/j.1365-2249.2000.01354.x

Cited by 17 publications

(11 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, the effects observed in the immunosuppressed group appear to be related to the treatment, rather than the underlying disease. This is in line with reports demonstrating that immunosuppressive agents such as corticosteroids impact on the number and maturation of airway DCs [8,35]. The finding that pDCs were more affected than mDCs might be due to the fact that pDCs are more susceptible to immunosuppressive therapies than mDCs [36].…”

Section: Discussionsupporting

confidence: 91%

Airway dendritic cell phenotypes in inflammatory diseases of the human lung

Lommatzsch¹,

Bratke²,

Bier³

et al. 2007

European Respiratory Journal

View full text Add to dashboard Cite

Airway dendritic cells (DCs) are key regulators of pulmonary immune responses. However, information is limited regarding the characteristics of airway DCs in human lung diseases.Plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) were analysed using four-colour flow cytometry in bronchoalveolar lavage fluid (BALF) from nonsmoking controls and patients with sarcoidosis, idiopathic pulmonary fibrosis (IPF) and pneumonia (in the presence or absence of immunosuppression).Compared with controls, immunocompetent patients with pneumonia displayed strongly enhanced pDC counts in BALF. In contrast, pDC counts in BALF from immunocompromised patients with pneumonia were even lower than in controls. This discrepancy was not explained by a different chemotactic milieu in the airways; all patients with pneumonia were characterised by strongly increased concentrations of the pDC-attracting chemokine, CXC chemokine ligand 10, in BALF. Patients with IPF were characterised by normal percentages of DC subtypes. However, the mDCs of patients with IPF were not as mature (CD83-positive) as those of controls. Patients with sarcoidosis displayed a unique increase in CD1a-negative mDCs in the airways. In addition, there was altered expression of costimulatory molecules (increased CD80 and decreased CD86 expression) on mDCs in patients with sarcoidosis.These data suggest that inflammatory diseases of the human lung are associated with a differential phenotype and recruitment of airway dendritic cells.

show abstract

Section: Discussionsupporting

confidence: 91%

Airway dendritic cell phenotypes in inflammatory diseases of the human lung

Lommatzsch¹,

Bratke²,

Bier³

et al. 2007

European Respiratory Journal

View full text Add to dashboard Cite

show abstract

“…Perhaps the capacity of GCS to influence the development of immune effector responses begins with their ability to modulate particular functions of APCs. GCS are known to inhibit the up-regulation of MHC class II molecules, the costimulatory molecules CD80 and CD86, as well as adhesion molecules and chemokine receptors on the DC surface during their maturation (65)(66)(67)(68). Our unique finding that CD11c ϩ DCs have the capacity to generate bioactive GCS via an intracrine mechanism would suggest a possible role for GCS modulation of DC maturation in vivo.…”

Section: Discussionmentioning

confidence: 83%

The Expression of 11β-Hydroxysteroid Dehydrogenase Type I by Lymphocytes Provides a Novel Means for Intracrine Regulation of Glucocorticoid Activities

Zhang

Ding

Daynes

2005

The Journal of Immunology

View full text Add to dashboard Cite

The 11β-hydroxysteroid dehydrogenase (11β-HSD) enzymes control the interconversion of active glucocorticoids (GCS) and their inactive 11-keto metabolites, a process commonly referred to as the cortisone/cortisol shuttle. Although the prereceptor metabolism of GCS by 11β-HSD is well documented in a variety of cells and tissues, it has not yet been carefully investigated in the major cell types of the immune system. In this study, we demonstrate that 11β-HSD1 transcripts, protein, and enzyme activities are actively expressed in murine CD4+, CD8+, and B220+ lymphocytes, as well as CD11c+ dendritic cells. Only reductase activity was observed in living cells, evidenced by the restricted conversion of cortisone to cortisol. Activation of CD4+ T cells increased their 11β-HSD1 activity, as did their polarization into Th1 or Th2 cells. CD4+ T cells isolated from aged donors (>16 mo) had increased 11β-HSD1 protein and an elevated capacity to convert cortisone to cortisol. The GCS generated in murine CD4+ T cells from their inactive 11-keto metabolites could activate the GCS receptor, demonstrated by an up-regulation of IL-7Rα and GCS-induced leucine zipper gene expression. The presence of a functional 11β-HSD1 provides lymphocytes with a novel intracrine regulatory mechanism that could influence such processes as lymphocyte development, effector function, and susceptibility to apoptosis. Thus, the presence of 11β-HSD1 provides an additional means to facilitate GCS influences over lymphocyte activities, uncoupled from the plasma concentration of GCS.

show abstract

“…On the basis of our previous experience using various hormones to generate veiled cells (12,13), the optimal concentration was determined to be that which resulted in the greatest number of cells displaying a veiled morphology. The optimal concentration for DHEA was found to be 10 26 M. In the case of DEX, we had previously carried out dose± response curves and have shown that although concentrations of 10 29 M were already effective, a concentration of 10 26 M added to DC obtained from bronchial alveolar lavage was optimal for obtaining a decreased function as well as a decrease in costimulatory molecule expression (29). We have therefore used 10 26 M DHEA and 10 26 M DEX in our subsequent experiments.…”

Section: Dhea and Dex Influence The Phenotype Of DC In Culturementioning

confidence: 99%

Opposing effects of dehydroepiandrosterone and dexamethasone on the generation of monocyte-derived dendritic cells

Canning

Grotenhuis

Wit

et al. 2000

European Journal of Endocrinology

View full text Add to dashboard Cite

Background: Dehydroepiandrosterone (DHEA) has been suggested as an immunostimulating steroid hormone, of which the effects on the development of dendritic cells (DC) are unknown. The effects of DHEA often oppose those of the other adrenal glucocorticoid, cortisol. Glucocorticoids (GC) are known to suppress the immune response at different levels and have recently been shown to modulate the development of DC, thereby influencing the initiation of the immune response. Variations in the duration of exposure to, and doses of, GC (particularly dexamethasone (DEX)) however, have resulted in conflicting effects on DC development. Aim: In this study, we describe the effects of a continuous high level of exposure to the adrenal steroid DHEA (10 26 M) on the generation of immature DC from monocytes, as well as the effects of the opposing steroid DEX on this development. Results: The continuous presence of DHEA (10 26 M) in GM-CSF/IL-4-induced monocyte-derived DC cultures resulted in immature DC with a morphology and functional capabilities similar to those of typical immature DC (T cell stimulation, IL-12/IL-10 production), but with a slightly altered phenotype of increased CD80 and decreased CD43 expression (markers of maturity).The continuous presence of DEX at a concentration of 10 26 M in the monocyte/DC cultures resulted in the generation of plastic-adherent macrophage-like cells in place of typical immature DC, with increased CD14 expression, but decreased expression of the typical DC markers CD1a, CD40 and CD80. These cells were strongly reactive to acid phosphatase, but equally capable of stimulating T cell proliferation as immature DC. The production of IL-12 by these macrophage-like cells was virtually shut down, whereas the production of IL-10 was significantly higher than that of control immature DC. Conclusion:The continuous presence of a high level of GC during the generation of immature DC from monocytes can modulate this development away from DC towards a macrophage-like cell. The combination of a low CD80 expression and a shutdown of IL-12 production suggests the possibility of DEX-generated cells initiating a Th2-biased response. These effects by DEX on DC development contrast with those by DHEA, which resulted in a more typical DC although possessing a phenotype possibly indicating a more mature state of the cell.

show abstract

Glucocorticoids hamper theex vivomaturation of lung dendritic cells from their low autofluorescent precursors in the human bronchoalveolar lavage: decreases in allostimulatory capacity and expression of CD80 and CD86

Cited by 17 publications

References 31 publications

Airway dendritic cell phenotypes in inflammatory diseases of the human lung

Airway dendritic cell phenotypes in inflammatory diseases of the human lung

The Expression of 11β-Hydroxysteroid Dehydrogenase Type I by Lymphocytes Provides a Novel Means for Intracrine Regulation of Glucocorticoid Activities

Opposing effects of dehydroepiandrosterone and dexamethasone on the generation of monocyte-derived dendritic cells

Contact Info

Product

Resources

About