Increased numbers of dendritic cells in the bronchial mucosa of atopic asthmatic patients: downregulation by inhaled corticosteroids

Möller, Gertrude M.; Overbeek, Shelley E.; Helden-Meeuwsen, Cornelia G van; Haarst, J. M. W. Van; Prens, E.P.; Mulder, Paul; Postma, Dirkje S.; Hoogsteden, H. C.

doi:10.1111/j.1365-2222.1996.tb00571.x

Cited by 166 publications

(37 citation statements)

References 36 publications

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“…In vivo studies also indicate that exposure to glucocorticoids is able to increase the numbers of (suppressor) macrophages (31,33). Our data are in line with such an effect, suggesting that the Mé/DC balance is affected by glucocorticoids, which skew this dynamic equilibrium in a macrophage direction when monocytes are continuously exposed to DEX during DC maturation.…”

Section: Discussionsupporting

confidence: 78%

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

Canning

Grotenhuis

Wit

et al. 2000

European Journal of Endocrinology

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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.

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Section: Discussionsupporting

confidence: 78%

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

Canning

Grotenhuis

Wit

et al. 2000

European Journal of Endocrinology

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“…27 Additionally, an increase in the level of respiratory mucosal DCs that expressed high affinity of IgE receptors has been reported both in allergic rhinitis and asthma conditions. 28 These findings strongly support that DCs have important roles in the pathogenesis and pathophysiology of atopic asthma.…”

Section: Discussionsupporting

confidence: 52%

A promoter nucleotide variant of the dendritic cell-specific DCNP1 associates with serum IgE levels specific for dust mite allergens among the Korean asthmatics

Kim

et al. 2007

Genes Immun

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Dendritic cells (DCs), the most abundant antigen-presenting cells in the lung, have been drawing attention for their roles in specific allergic responses to aeroallergens with support of Th lymphocytes, and in persistent inflammatory changes in allergic asthma. To identify genetic factors that may be involved in the asthma susceptibility and development of the disease phenotypes, we examined association of DC-specific DCNP1 polymorphisms with the disease risk. The case-control study revealed association of the nucleotide variants with serum immunoglobulin E (IgE) levels specific for Dermatophagoides farinae (Der f 1) and Dermatophagoides pteronyssinus (Der p 1), major aeroallergens of dust mites, among subjects with asthma. In particular, the T-allele-carrying genotype frequencies for one of the variants (c.À1289C4T) located in the promoter region were found increased in the asthmatic group with low levels of the mite-specific IgE (odds ratio (OR) ¼ 0.63 (0.48-0.83) for Der p 1). Results from functional analyses indicated that the promoter variant would affect the gene expression by modulating DNA-protein interaction. We propose that the genetic polymorphism of DCNP1 may influence production of specific IgE by altering DC functions in the mite allergen presenting and/or processing. The functional relevance of the genetic variation would provide an important insight into the genetic basis of allergic response to the mite antigens.

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“…This enriched population of DC precursors provides a readily available source to replenish pulmonary DC, both as part of the normal turnover of these cells and during inflammatory reactions (25,27). In this study, we showed that airway epithelium controls the mobilization of these DC precursors through chemokine secretion.…”

Section: Discussionmentioning

confidence: 67%

Impact of Bronchial Epithelium on Dendritic Cell Migration and Function: Modulation by the Bacterial Motif KpOmpA

Pichavant

Taront

Jeannin

et al. 2006

The Journal of Immunology

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Mucosal immune response depends on the surveillance network established by dendritic cells (DC), APC localized within the epithelium. Bronchial epithelial cells (BEC) play a pivotal role both in the host defense and in the pathogenesis of inflammatory airway disorders. We previously showed that the outer membrane protein A from Klebsiella pneumoniae (KpOmpA), a pathogen-associated molecular pattern (PAMP) derived from Klebsiella pneumoniae, activates BEC. In this study, we evaluated the consequences of this activation on DC traffic and functions. KpOmpA significantly increased the production of CCL2, CCL5, CXCL10, and CCL20 by BEC. Stimulation of BEC increased their chemotactic activity for monocyte-derived DC (MDDC) precursors, through CCL5 and CXCL10 secretion. BEC/MDDC precursor coculture leads to an ICAM-1-dependent accelerated differentiation and enhanced maturation of MDDC. BEC/DC interactions did not affect the capacity of DC to induce T cell proliferation. However, DC preincubated with BEC increased significantly the IL-10 production by autologous T cells. Basolateral and intraepithelial DC differently enhance IL-4 and/or IL-10 synthesis according to the condition of stimulation. In vivo, intranasal injections of KpOmpA into BALB/c mice induced the recruitment of CD11c+ and I-Ad+ myeloid DC associated with bronchial epithelium activation as evidenced by CCL20 expression. These data show that KpOmpA-exposed BEC participate in the homeostasis of myeloid DC network, and regulate the induction of local immune response.

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Increased numbers of dendritic cells in the bronchial mucosa of atopic asthmatic patients: downregulation by inhaled corticosteroids

Abstract: Our data suggest that dendritic cells are involved in asthmatic inflammation and that corticosteroids may downregulate the number of dendritic.

Cited by 166 publications

References 36 publications

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

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

A promoter nucleotide variant of the dendritic cell-specific DCNP1 associates with serum IgE levels specific for dust mite allergens among the Korean asthmatics

Impact of Bronchial Epithelium on Dendritic Cell Migration and Function: Modulation by the Bacterial Motif KpOmpA

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