Airway epithelial cells regulate the functional phenotype of locally differentiating dendritic cells: implications for the pathogenesis of infectious and allergic airway disease.
TL;DR: It is suggested that resting AECs modulate local DC differentiation to optimize antimicrobial defenses in the airways and in the process down-modulate capacity for expression of potentially damaging Th2 immunity.
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Abstract: Atopic asthma pathogenesis is driven by the combined effects of airway inflammation generated during responses to viral infections and aeroallergens, and both these pathways are regulated by dendritic cells (DC) that differentiate locally from monocytic precursors. These DCs normally exhibit a sentinel phenotype characterized by active Ag sampling but attenuated presentation capability, which limits the intensity of local expression of adaptive immunity. How this tight control of airway DC functions is normally maintained, and why it breaks down in some atopics leading to immunopathological changes in airway tissues, is unknown. We postulated that signals from adjacent airway epithelial cells (AEC) contribute to regulation of local differentiation of DC. We tested this in a coculture model containing both cell types in a GM-CSF-IL-4-enriched cytokine milieu characteristic of the atopic asthmatic airway mucosa. We demonstrate that contact with AEC during DC differentiation up-regulates expression of the function-associated markers MHC class II, CD40, CD80, TLR3, and TLR4 on DCs with concomitant up-regulation of Ag uptake/processing. Moreover, the AEC-conditioned DCs displayed increased LPS responsiveness evidenced by higher production of IL-12, IL-6, IL-10, and TNF-α. The Th2 memory-activating properties of AEC-conditioned DCs were also selectively attenuated. Data from microarray and blocking experiments implicate AEC-derived type 1 IFNs and IL-6 in modulation of DC differentiation. Collectively, these findings suggest that resting AECs modulate local DC differentiation to optimize antimicrobial defenses in the airways and in the process down-modulate capacity for expression of potentially damaging Th2 immunity.
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Citations
Effect of Polarization on Airway Epithelial Conditioning of Monocyte-Derived Dendritic Cells
Dick Papazian,Tashi Chhoden,Maria Arge,Thomas Vorup-Jensen,Claus Henrik Nielsen,Kaare Lund,Peter Adler Würtzen,Søren Hansen +7 more
TL;DR: It is determined that AEC conditioning favoring cellular integrity leads to a tolerogenic MDDC phenotype, which is likely to be important in regulating immune responses against commonly inhaled allergens.
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Cell-contact dependent inhibition of monocytes by airway epithelial cells and reversion by infection with Respiratory Syncytial Virus.
Mustapha Oumouna,Michael Weitnauer,Vedrana Mijošek,Lotte M. Schmidt,Tatjana Eigenbrod,Alexander H. Dalpke +5 more
TL;DR: It is concluded that airway epithelial cells control the reactivity of monocytes through direct and indirect interactions; however tonic inhibition can be reverted upon stimulation of AECs with RSV and thereof derived molecular patterns.
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Monocyte differentiation toward regulatory dendritic cells is not affected by respiratory syncytial virus-induced inflammatory mediators.
Koenraad F. van der Sluijs,Carolina Obregon,Thomas Geiser,Kathrin Mühlemann,Laurent P. Nicod +4 more
TL;DR: Airway epithelial cells maintain an important suppressive DC phenotype under the inflammatory conditions induced by infection with RSV, indicating that the airway epithelium maintains an antiviral response by the release of Type I IFN.
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Can Specific IgE Discriminate between Intrinsic and Atopic Asthma
TL;DR: The authors attempted to determine a potential mechanism for the failure of allergen challenge in subjects with intrinsic asthma to lead to a decreased FEV1, and focused on the ability of dust mite allerGEN to activate basophils from either intrinsic or atopic asthma donors, when cultured with sputum from these subjects.
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References
Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles
Aravind Subramanian,Pablo Tamayo,Vamsi K. Mootha,Sayan Mukherjee,Benjamin L. Ebert,Michael A. Gillette,Amanda G. Paulovich,Scott L. Pomeroy,Todd R. Golub,Eric S. Lander,Jill P. Mesirov +10 more
TL;DR: The Gene Set Enrichment Analysis (GSEA) method as discussed by the authors focuses on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation.
Dendritic cells and the control of immunity
TL;DR: Once a neglected cell type, dendritic cells can now be readily obtained in sufficient quantities to allow molecular and cell biological analysis and the realization that these cells are a powerful tool for manipulating the immune system is realized.
15.2K
Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments
TL;DR: The hierarchical model of Lonnstedt and Speed (2002) is developed into a practical approach for general microarray experiments with arbitrary numbers of treatments and RNA samples and the moderated t-statistic is shown to follow a t-distribution with augmented degrees of freedom.
Immunobiology of Dendritic Cells
Jacques Banchereau,Francine Brière,Christophe Caux,Jean Davoust,Serge Lebecque,Yong-Jun Liu,Bali Pulendran,Karolina Palucka +7 more
TL;DR: Dendritic cells are antigen-presenting cells with a unique ability to induce primary immune responses and may be important for the induction of immunological tolerance, as well as for the regulation of the type of T cell-mediated immune response.
7.2K
Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha.
TL;DR: Cultured DCs are as efficient as antigen-specific B cells in presenting tetanus toxoid (TT) to specific T cell clones and their efficiency of antigen presentation can be further enhanced by specific antibodies via FcR- mediated antigen uptake.
5.5K