Dendritic Cells as Regulators of the Immune Response to Inhaled Allergen: Recent Findings in Animal Models of Asthma

Lambrecht, Bart N.; Hoogsteden, Henk C.; Pauwels, Romain

doi:10.1159/000053778

Cited by 24 publications

(22 citation statements)

References 100 publications

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“…In addition, it has been shown that epithelial cells of the human upper and lower respiratory tract can internalize and process antigens through pathways that lead to presentation in the context of HLA-DR and to T cell activation, providing further support to the view that these cells can play a role in local immune responses in proximal airway regions (34). This activity would be presumed to be separate from processes involved with initial presentation of antigen to naïve, CD45RAϩ T cells, a domain of activity relegated to professional antigen-presenting cells, such as DCs, which takes place primarily within lymphoid tissues (19,28).…”

Section: Dose-response Characteristics Of B7-h2 and B7-h3 To Treatmenmentioning

confidence: 84%

Expression of genes for B7-H3 and other T cell ligands by nasal epithelial cells during differentiation and activation

Saatian¹,

Yu²,

Lane³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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Epithelial cells of the human respiratory tract express human leukocyte antigen (HLA) and the costimulatory molecules B7-1 and B7-2. Little is known, however, about the constitutive expression of genes encoding for the more recently identified members of the B7 homolog family of costimulatory molecules or about the influence of cellular differentiation and cytokines on their activity or on that of HLA or B7-1 and B7-2. Human nasal epithelial (HNE) cells were grown at the air-liquid interface (ALI) for 2 or 21 days to model in vivo conditions. Expression of genes for HLA-B and HLA-DR1 increased during mucociliary differentiation during this period and became more similar to HNE cells obtained fresh by brush biopsy from nasal turbinates. Gene transcripts for B7-H3 and B7-H2 were abundantly expressed in cells cultured at the ALI, but neither their activities nor that of B7-2 was significantly altered during differentiation. IFN-gamma and TNF-alpha upregulated mRNA encoding for both HLA molecules, but not for the B7 molecules. This study describes, for the first time, the expression of B7-H3 and B7-H2 by HNE cells and thus expands the range of potential costimulatory signals through which these cells may interact with activated mucosal T lymphocytes. In addition, the results suggest that the extent of mucociliary differentiation of cultured cells may influence this capability

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Section: Dose-response Characteristics Of B7-h2 and B7-h3 To Treatmenmentioning

confidence: 84%

Expression of genes for B7-H3 and other T cell ligands by nasal epithelial cells during differentiation and activation

Saatian¹,

Yu²,

Lane³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…There is abundant expression of MHC class II molecules within the airways and alveoli (18). There are professional as well as nonprofessional antigen-presenting cells present in airways and lungs (18,19,29,53,99). The airways are also lined with the bronchus-associated lymphatic (21,72).…”

Section: Discussionmentioning

confidence: 99%

Intranasal Exposure to Bacterial Superantigens Induces Airway Inflammation in HLA Class II Transgenic Mice

Rajagopalan¹,

Izutsu²,

Singh³

et al. 2006

Infect Immun

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Staphylococcus aureus is widely prevalent in the nasopharynges of healthy individuals (carriers) but can also cause serious infections. S. aureus can elaborate a variety of superantigen exotoxins in "carrier" or "pathogenic" states. Streptococcus pyogenes can also colonize the nasopharynx and elaborate superantigens. Unlike the acute effects of superantigen exotoxins absorbed through the gut or vaginal mucosa, little is known regarding the pathogenesis of superantigens entering through the intranasal route. In the current study, we evaluated the local and systemic effects of staphylococcal enterotoxin B (SEB) and streptococcal pyrogenic exotoxin A (SPEA) delivered through the intranasal route. Superantigens were administered intranasally on multiple occasions, and experimental animals were sacrificed on day 8 for experimental analyses. SEB-induced airway inflammation was more pronounced for HLA-DR3 transgenic mice than for BALB/c mice, consistent with bacterial superantigens binding more efficiently to human than murine major histocompatibility complex class II. The nature of the airway inflammation in HLA-DR3 mice was determined by the concentration of SEB applied intranasally. Low concentrations (20 ng) induced eosinophilic airway inflammation as well as eosinophil degranulation, whereas intranasal exposure to higher concentrations (2,000 ng) resulted in neutrophilic airway inflammation, permanent airway destruction, toxic shock, and mortality. SEB-induced eosinophilic inflammatory response was enhanced in signal transducer and activator of transcription (STAT)-4-deficient HLA-DQ8 transgenic mice with defective interleukin-12 signaling. Intranasal administration of SPEA induced airway inflammation and systemic immune activation in HLA-DQ8 transgenic mice. In conclusion, repeated chronic intranasal exposure to bacterial superantigens causes airway inflammation and systemic immune activation.

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“…Research since the late 1980s has shown an important role for DCs in pulmonary immune responses (3,(5)(6)(7)(8)(9)(10)(11)(12)(13). DCs are present in high density in the proximal airways and are well positioned to capture Ags.…”

Section: Endritic Cells (Dcs)mentioning

confidence: 99%

Distinct Responses of Lung and Spleen Dendritic Cells to the TLR9 Agonist CpG Oligodeoxynucleotide

Chen

Arora

Yarlagadda

et al. 2006

The Journal of Immunology

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Dendritic cells (DCs) sense various components of invading pathogens via pattern recognition receptors such as TLRs. CpG oligodeoxynucleotides (ODNs), which mimic bacterial DNA, inhibit allergic airways disease and promote responses in the spleen to bacterial components. Because many TLR agonists are currently being tested for potential therapeutic effects, it is important to characterize the expression and function of TLRs in different tissues. We show that both myeloid and plasmacytoid DCs in the spleen express TLR9, the receptor for CpG ODNs, but lung DCs show no detectable expression in either subset. TLR4 expression in contrast was detected on both lung and spleen DCs. LPS was superior to CpG ODN in increasing the allostimulatory potential of lung DCs and their expression of CD40. However, both agonists efficiently stimulated spleen DCs. CpG ODNs administered to mice efficiently inhibited Th2 cytokine production both in the lung draining lymph node and in the spleen. Surprisingly, inhibition of Th2 cytokine production was evident despite high levels of expression of GATA-3 and additional transcription factors that regulate Th2 responses. Although in the spleen CpG ODNs induced IL-6, a key cytokine induced via TLR9-MyD88 signaling, no IL-6 was detectable in lung LN cells. These studies show for the first time that lung DCs lack TLR9 expression, but, despite this deficiency, CpG ODNs induce potent inhibitory effects on Th2 cytokine production in the lung without inducing expression of the proinflammatory cytokine, IL-6, which has been linked to chronic diseases in the lung and the gut.

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Dendritic Cells as Regulators of the Immune Response to Inhaled Allergen: Recent Findings in Animal Models of Asthma

Cited by 24 publications

References 100 publications

Expression of genes for B7-H3 and other T cell ligands by nasal epithelial cells during differentiation and activation

Expression of genes for B7-H3 and other T cell ligands by nasal epithelial cells during differentiation and activation

Intranasal Exposure to Bacterial Superantigens Induces Airway Inflammation in HLA Class II Transgenic Mice

Distinct Responses of Lung and Spleen Dendritic Cells to the TLR9 Agonist CpG Oligodeoxynucleotide

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