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Committed mast cell progenitors in mouse blood differ in maturity between Th1 and Th2 strains
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.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
2013 (English)In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 68, no 10, 1333-1337 p.Article in journal (Refereed) Published
Abstract [en]

Mast cell progenitors (MCp) leave the bone marrow and migrate to peripheral tissues where they mature. Although the existence of committed MCp in adult mouse and human blood has been postulated, they have never been found. We have isolated a rare population of cells in adult mouse blood, committed to the mast cell lineage. These were identified as lineage c-kithi ST2+ integrin β7hi CD16/32hi cells. Moreover, a major difference in maturity of these cells based on FcεRI expression was observed between the Th2-prone BALB/c strain and the Th1-prone C57BL/6 strain (66% vs 25% FcεRI+, respectively). Therefore, the choice of mouse strain is critical when studying disease models such as experimental asthma where mast cells and their progenitors are involved.

Place, publisher, year, edition, pages
2013. Vol. 68, no 10, 1333-1337 p.
National Category
Immunology Immunology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-205507DOI: 10.1111/all.12223ISI: 000326024300015OAI: oai:DiVA.org:uu-205507DiVA: diva2:644702
Available from: 2013-09-02 Created: 2013-08-19 Last updated: 2017-12-06Bibliographically 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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