Monitoring C5AR2 expression using a floxed tdtomato-C5AR2 knock-in mouse

Karsten, Christian M., Wiese, Anna V., Mey, Fabian, Figge, Julia, Woodruff, Trent M., Reuter, Tom, Scurtu, Olga, Kordowski, Anna, Almeida, Larissa N., Briukhovetska, Daria, Quell, Katharina M., Sun, Jing, Ender, Fanny, Schmudde, Inken, Vollbrandt, Tillman, Laumonnier, Yves and Köhl, Jörg (2017) Monitoring C5AR2 expression using a floxed tdtomato-C5AR2 knock-in mouse. Journal of Immunology, 199 9: 3234-3248. doi:10.4049/jimmunol.1700710

Author Karsten, Christian M.
Wiese, Anna V.
Mey, Fabian
Figge, Julia
Woodruff, Trent M.
Reuter, Tom
Scurtu, Olga
Kordowski, Anna
Almeida, Larissa N.
Briukhovetska, Daria
Quell, Katharina M.
Sun, Jing
Ender, Fanny
Schmudde, Inken
Vollbrandt, Tillman
Laumonnier, Yves
Köhl, Jörg
Title Monitoring C5AR2 expression using a floxed tdtomato-C5AR2 knock-in mouse
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 1550-6606
Publication date 2017-11-01
Year available 2017
Sub-type Article (original research)
DOI 10.4049/jimmunol.1700710
Open Access Status Not yet assessed
Volume 199
Issue 9
Start page 3234
End page 3248
Total pages 15
Place of publication Bethesda, MD United States
Publisher American Association of Immunologists
Language eng
Subject 2403 Immunology
Abstract The biological significance of C5a receptor [(C5aR)2/C5L2], a seven-transmembrane receptor binding C5a and C5adesArg, remains ill-defined. Specific ligation of C5aR2 inhibits C5a-induced ERK1/2 activation, strengthening the view that C5aR2 regulates C5aR1- mediated effector functions. Although C5aR2 and C5aR1 are often coexpressed, a detailed picture of C5aR2 expression in murine cells and tissues is still lacking. To close this gap, we generated a floxed tandem dye (td)Tomato-C5aR2 knock-in mouse that we used to track C5aR2 expression in tissue-residing and circulating immune cells. We found the strongest C5aR2 expression in the brain, bone marrow, and airways. All myeloid-derived cells expressed C5aR2, although with different intensities. C5aR2 expression in blood and tissue neutrophils was strong and homogeneous. Specific ligation of C5aR2 in neutrophils from tdTomato-C5aR2 mice blocked C5a-driven ERK1/2 phosphorylation, demonstrating functionality of C5aR2 in the reporter mice. In contrast to neutrophils, we found tissue-specific differences in C5aR2 expression in eosinophils, macrophages, and dendritic cell subsets. Naive and activated T cells stained negative for C5aR2, whereas B cells from different tissues homogeneously expressed C5aR2. Also, NK cell subsets in blood and spleen strongly expressed C5aR2. Activation of C5aR2 in NK cells suppressed IL-12/IL-18-induced IFN-g production. Intratracheal IL-33 challenge resulted in decreased C5aR2 expression in pulmonary eosinophils and monocytederived dendritic cells. In summary, we provide a detailed map of murine C5aR2 immune cell expression in different tissues under steady-state conditions and upon pulmonary inflammation. The C5aR2 knock-in mouse will help to reliably track and conditionally delete C5aR2 expression in experimental models of inflammation.
Keyword Experimental Allergic-Asthma
Dendritic Cells
Complement Receptors
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1911
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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School of Biomedical Sciences Publications
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Created: Fri, 03 Nov 2017, 09:05:36 EST