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

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 (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Journal of Immunology American Association of Immunologists

Book Volume: 202

Article Number: 1099-1111

Journal Issue: 4

DOI: 10.4049/jimmunol.1800269

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.

Authors with CRIS profile

Sarah Cunningham Department of Transfusion Medicine and Haemostaseology Holger Hackstein Professur für Transfusionsmedizin und Cell-Engineering

Involved external institutions

Justus-Liebig-Universität Gießen DE Germany (DE) Freie Universität Berlin DE Germany (DE) Goethe-Universität Frankfurt am Main DE Germany (DE) Philipps-Universität Marburg DE Germany (DE)

How to cite

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).

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