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CD11c(+) Cells Are Required for Antigen-Induced Increase of Mast Cells in the Lung
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Statens veterinärmedicinska anstalt.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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2012 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 189, no 8, 3869-3877 p.Article in journal (Refereed) Published
Abstract [en]

Patients with allergic asthma have more lung mast cells, which likely worsens the symptoms. In experimental asthma, CD11c(+) cells have to be present during the challenge phase for several features of allergic inflammation to occur. Whether CD11c(+) cells play a role for Ag-induced increases of lung mast cells is unknown. In this study, we used diphtheria toxin treatment of sensitized CD11c-diphtheria toxin receptor transgenic mice to deplete CD11c(+) cells. We demonstrate that recruitment of mast cell progenitors to the lung is substantially reduced when CD11c(+) cells are depleted during the challenge phase. This correlated with an impaired induction of endothelial VCAM-1 and led to a significantly reduced number of mature mast cells 1 wk after challenge. Collectively, these data suggest that Ag challenge stimulates CD11c(+) cells to produce cytokines and/or chemokines required for VCAM-1 upregulation on the lung endothelium, which in turn is crucial for the Ag-induced mast cell progenitor recruitment and the increase in mast cell numbers.

Place, publisher, year, edition, pages
2012. Vol. 189, no 8, 3869-3877 p.
National Category
Immunology Immunology in the medical area
Research subject
Immunology
Identifiers
URN: urn:nbn:se:uu:diva-184515DOI: 10.4049/jimmunol.1201200ISI: 000309590900014PubMedID: 22972929OAI: oai:DiVA.org:uu-184515DiVA: diva2:565594
Funder
Swedish Research Council
Available from: 2012-11-07 Created: 2012-11-07 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Mast Cell Progenitor Trafficking in Allergic Airway Inflammation
Open this publication in new window or tab >>Mast Cell Progenitor Trafficking in Allergic Airway Inflammation
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Mast cell progenitors originate from the bone marrow and migrate to the lungs via the blood. During maturation, these cells acquire granules that contain a potent array of bronchoconstrictive mediators. The number of pulmonary mast cells is augmented in asthmatic patients and in mice with allergic airway inflammation, possibly contributing to airway hyperreactivity. An increase in mast cells is likely due to an increased recruitment of committed mast cell progenitors from the blood. However, until now a committed mast cell progenitor population has not been found in adult peripheral blood. We isolated Lin- c-kithi ST2+ integrin β7hi CD16/32hi progenitors from murine blood and showed that these cells were committed to the mast cell lineage. Based on the expression of FcεRI, these cells were less mature in Th1-prone C57BL/6 mice than in Th2-prone BALB/c mice.

Asthma is associated with elevated levels of IgE. Upon exposure to allergens, IgE immune complexes are formed. In a mouse model of allergic airway inflammation, we showed that intranasal administration of IgE immune complexes to antigen-sensitized mice resulted in an increased number of mast cell progenitors compared with antigen administration alone. The increase in mast cell progenitors was independent of the low-affinity IgE receptor CD23. Rather, signaling through the common FcRγ-chain was required to enhance the number of lung mast cell progenitors. Signaling through FcεRI was likely responsible for the increase. However a role for FcγRIV could not be excluded.

CD11c+ cells, such as dendritic cells, are important for antigen sensitization. In a mouse model of allergic airway inflammation, these cells are also important for the development of airway hyperreactivity, eosinophilia and Th2 cytokine production in response to antigen challenge. We showed that CD11c+ cells are critical for the recruitment of lung mast cell progenitors and the subsequent increase in mast cells. These CD11c+ cells were needed for the upregulation of endothelial vascular cell adhesion molecule-1 (VCAM-1), which is a prerequisite for the antigen-induced recruitment of lung mast cell progenitors.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 41 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 932
Keyword
Mast cells, mast cell progenitors, allergy, asthma, allergic airway inflammation, IgE, lung, CD11c
National Category
Immunology
Identifiers
urn:nbn:se:uu:diva-206608 (URN)978-91-554-8741-6 (ISBN)
Public defence
2013-10-17, C8:301, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2013-09-24 Created: 2013-09-02 Last updated: 2014-01-23

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Dahlin, Joakim SHeyman, BirgittaHallgren, Jenny

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