Mast Cells Induce Migration of Dendritic Cells in a Murine Model of Acute Allergic Airway Disease

Reuter, Sebastian; Dehzad, Nina; Martin, Helen; Heinz, A.; Castor, Timo; Sudowe, Stephan; Reske‐Kunz, Angelika B.; Stassen, Michael; Buhl, Roland; Taube, Christian

doi:10.1159/000242359

Cited by 25 publications

(29 citation statements)

References 50 publications

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“…In the current study, we show that a ligand [poly(I:C)] for the TLR3 receptor, which recognizes ssRNA, or a ligand for TLR7/8 receptor (R848), which recognizes dsRNA, also induces enhanced migration of Ag-exposed cDCs from the lung to the draining lymph nodes in comparison with that in animals only treated with Ag. Similar to previous studies, the highest number of fluorescent DCs in the draining lymph node were detectable 24 h after allergen application (27). Increased DC migration has been described in animals exposed to influenza virus, which also leads to immune responses to simultaneously inhaled allergen (8,28).…”

Section: Discussionsupporting

confidence: 87%

TLR3 but Not TLR7/8 Ligand Induces Allergic Sensitization to Inhaled Allergen

Reuter¹,

Dehzad²,

Martin³

et al. 2012

The Journal of Immunology

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Epidemiological studies suggest that viral infections during childhood are a risk factor for the development of asthma. However, the role of virus-specific pattern recognition receptors in this process is not well defined. In the current study, we compare the effects of the inhaled viral TLR ligands polyinosinic-polycytidylic acid (TLR3) and resiquimod (TLR7/8) on sensitization to a model allergen (OVA) in a murine model. Both compounds enhance the migration, activation, and Ag-processing of myeloid dendritic cells from the lung to the draining lymph nodes comparable to the effects of LPS. Application of polyinosinic-polycytidylic acid [poly(I:C)] or LPS induces production of allergen-specific IgE and IgG1, whereas resiquimod (R848) had no effect. In addition, rechallenge of mice with OVA resulted in airway inflammation and mucus production in animals that received either poly(I:C) or LPS but not after application of R848. In summary, these results show that activation of TLR3 in combination with inhaled allergen results in induction of dendritic cell activation and migration similar to the effects of LPS. This leads to the development of allergic airway disease after allergen rechallenge, whereas mice treated with R848 did not develop allergic airway disease. These findings give further insight into the effects of stimulation of different TLRs on the development of asthma.

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Section: Discussionsupporting

confidence: 87%

TLR3 but Not TLR7/8 Ligand Induces Allergic Sensitization to Inhaled Allergen

Reuter¹,

Dehzad²,

Martin³

et al. 2012

The Journal of Immunology

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“…1). Similar to previous results (26), the numbers of fluorescent DCs peaked at 24 h after the application of labeled Ag (Fig. 6B, 6C).…”

Section: Wnt Overexpression Does Not Affect Induction Of Tregs But Dosupporting

confidence: 90%

“…injection of ketamine/rompun (Ketamin-ratiopharm; Ratiopharm, Ulm, Germany/Rompun 2%; Bayer, Leverkusen, Germany) and received a single intranasal (i.n.) application of fluorescence-labeled OVA derivate (OVA Alexa Fluor 647; MoBiTec, Göttingen, Germany) dissolved in 40 ml PBS (26,27). At 12,24, and 48 h following treatment, regional lymph nodes were collected and analyzed via FACS for OVA + cells.…”

Section: Experimental Protocolsmentioning

confidence: 99%

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The Wnt/β-Catenin Pathway Attenuates Experimental Allergic Airway Disease

Reuter

Martin

Beckert

et al. 2014

The Journal of Immunology

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Signaling via the Wnt/β-catenin pathway plays crucial roles in embryogenesis and homeostasis of adult tissues. In the lung, the canonical Wnt/β-catenin pathway has been implicated in remodeling processes, development of emphysema, and fibrosis. However, its relevance for the modulation of allergic responses in the lung remains unclear. Using genetically modified mice with lung-specific inducible (doxycycline) Wnt-1 expression (CCSP-rtTA × tetO-Wnt1), the impact of Wnt on the development of allergic airway disease was analyzed. Overexpression of Wnt during the allergen challenge phase attenuated the development of airway inflammation in an acute model, as well as in a more therapeutic model of secondary challenge. These findings were further supported by treatment of allergen-sensitized mice with LiCl during challenge. Similar to Wnt, LiCl prevented the degradation of β-catenin and, thus, attenuated allergic airway inflammation and hyperresponsiveness. Migration studies revealed that lung-specific expression of Wnt reduced the migration of Ag-loaded dendritic cells (DCs) into the draining lymph nodes following allergen challenge. Administration of in vitro allergen-loaded DCs overcame Wnt-mediated suppression of airway inflammation. Furthermore, in vitro studies confirmed that DC-dependent T cell activation is impaired by blocking β-catenin degradation. These results demonstrate an important role for the canonical Wnt/β-catenin pathway in the DC-mediated regulation of allergic responses in the lung.

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“…[28][29][30][31] In these sensitized individuals, exposure with the allergen results in specific immunological responses in the lung, in which mast cells and DCs modulate the adaptive immune responses, which is characterized by a Th2 response, including IL-4, IL-5, and IL-13, and accumulation of eosinophilic granulocytes in the airway wall and lumen. [32][33][34][35] If these immune responses persist in the airway wall, structural changes, such as goblet cell metaplasia, basement membrane thickening, hypertrophy of ASM, and subepithelial fibrosis, can occur and these structural changes are summarized under the term airway remodeling. 2 …”

Section: Cell Populations Involved In Airway Inflammationmentioning

confidence: 99%

Take the Wnt out of the inflammatory sails: modulatory effects of Wnt in airway diseases

Reuter

Beckert

Taube

2016

Laboratory Investigation

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Bronchial asthma and chronic obstructive pulmonary disease (COPD) are chronic diseases that are associated with inflammation and structural changes in the airways and lungs. Recent findings have implicated Wnt pathways in critically regulating inflammatory responses, especially in asthma. Furthermore, canonical and noncanonical Wnt pathways are involved in structural changes such as airway remodeling, goblet cell metaplasia, and airway smooth muscle (ASM) proliferation. In COPD, Wnt pathways are not only associated with structural changes in the airways but also involved in the development of emphysema. The present review summarizes the role and function of the canonical and noncanonical Wnt pathway with regard to airway inflammation and structural changes in asthma and COPD. Further identification of the role and function of different Wnt molecules and pathways could help to develop novel therapeutic options for these diseases.

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Mast Cells Induce Migration of Dendritic Cells in a Murine Model of Acute Allergic Airway Disease

Cited by 25 publications

References 50 publications

TLR3 but Not TLR7/8 Ligand Induces Allergic Sensitization to Inhaled Allergen

TLR3 but Not TLR7/8 Ligand Induces Allergic Sensitization to Inhaled Allergen

The Wnt/β-Catenin Pathway Attenuates Experimental Allergic Airway Disease

Take the Wnt out of the inflammatory sails: modulatory effects of Wnt in airway diseases

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