ADAR1 Is Required for Dendritic Cell Subset Homeostasis and Alveolar Macrophage Function

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Baal N, Cunningham S, Obermann HL, Thomas J, Lippitsch A, Dietert K, Gruber AD, Kaufmann A, Michel G, Nist A, Stiewe T, Rupp O, Goesmann A, Zukunft S, Fleming I, Bein G, Lohmeyer J, Bauer S, Hackstein H
Zeitschrift: Journal of Immunology
Jahr der Veröffentlichung: 2019
Band: 202
Heftnummer: 4
ISSN: 0022-1767


Abstract

RNA editing by adenosine deaminases acting on dsRNA (ADAR) has become of increasing medical relevance, particularly because aberrant ADAR1 activity has been associated with autoimmunity and malignancies. However, the role of ADAR1 in dendritic cells (DC), representing critical professional APCs, is unknown. We have established conditional murine CD11c Cre-mediated ADAR1 gene ablation, which did not induce general apoptosis in CD11c(+) cells but instead manifests in cell type-specific effects in DC subpopulations. Bone marrow-derived DC subset analysis revealed an incapacity to differentiate CD103 DC+ in both bulk bone marrow and purified pre-DC lineage progenitor assays. ADAR1 deficiency further resulted in a preferential systemic loss of CD8(+)/CD103(+) DCs, revealing critical dependency on ADAR1, whereas other DC subpopulations were moderately affected or unaffected. Additionally, alveolar macrophages were depleted and dysfunctional, resembling pulmonary alveolar proteinosis. These results reveal an unrecognized role of ADAR1 in DC subset homeostasis and unveils the cell type-specific effects of RNA editing.


FAU-Autoren / FAU-Herausgeber

Hackstein, Holger Prof. Dr. med.
Professur für Transfusionsmedizin und Cell-Engineering


Autor(en) der externen Einrichtung(en)
Freie Universität Berlin
Goethe-Universität Frankfurt am Main
Justus-Liebig-Universität Gießen
Philipps-Universität Marburg


Zitierweisen

APA:
Baal, N., Cunningham, S., Obermann, H.-L., Thomas, J., Lippitsch, A., Dietert, K.,... Hackstein, H. (2019). ADAR1 Is Required for Dendritic Cell Subset Homeostasis and Alveolar Macrophage Function. Journal of Immunology, 202(4). https://dx.doi.org/10.4049/jimmunol.1800269

MLA:
Baal, Nelli, et al. "ADAR1 Is Required for Dendritic Cell Subset Homeostasis and Alveolar Macrophage Function." Journal of Immunology 202.4 (2019).

BibTeX: 

Zuletzt aktualisiert 2019-22-02 um 11:23