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Recombination Activating Gene-2 Regulates CpG-Mediated Interferon-α Production in Mouse Bone Marrow-Derived Plasmacytoid Dendritic Cells

Luo, Xin M. and Lei, Margarida Y. Y. (2012) Recombination Activating Gene-2 Regulates CpG-Mediated Interferon-α Production in Mouse Bone Marrow-Derived Plasmacytoid Dendritic Cells. PLoS ONE, 7 (10). Art. No. e47952. ISSN 1932-6203. PMCID PMC3480463. https://resolver.caltech.edu/CaltechAUTHORS:20121203-103239494

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Abstract

Using mice that lack recombination activating gene-2 (Rag2), we have found that bone marrow-derived plasmacytoid dendritic cells (pDCs) as main producers of interferon-α (IFNα) require Rag2 for normal development. This is a novel function for Rag2, whose classical role is to initiate B and T cell development. Here we showed that a population of common progenitor cells in the mouse bone marrow possessed the potential to become either B cells or pDCs upon appropriate stimulations, and the lack of Rag2 hindered the development of both types of progeny cells. A closer look at pDCs revealed that Rag2^(−/−) pDCs expressed a high level of Ly6C and were defective at producing IFNα in response to CpG, a ligand for toll-like receptor 9. This phenotype was not shared by Rag1^(−/−) pDCs. The induction of CCR7, CD40 and CD86 with CpG, however, was normal in Rag2^(−/−) pDCs. In addition, Rag2^(−/−) pDCs retained the function to promote antibody class switching and plasma cell formation through producing IL-6. Further analysis showed that interferon regulatory factor-8, a transcription factor important for both IFNα induction and pDC development, was dysregulated in pDCs lacking Rag2. These results indicate that the generation of interferon response in pDCs requires Rag2 and suggest the lymphoid origin of bone marrow-derived pDCs.


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http://dx.doi.org/10.1371/journal.pone.0047952DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480463/PubMed CentralArticle
Additional Information:© 2012 Luo and Lei. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received: July 5, 2012; Accepted: September 18, 2012; Published: October 24, 2012. This study was financially supported by Dr. David Baltimore at California Institute of Technology through various grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Dr. David Baltimore at California Institute of Technology for his invaluable guidance and generous support in providing the infrastructure required for the completion of this study. Author Contributions: Conceived and designed the experiments: XL. Performed the experiments: XL ML. Analyzed the data: XL ML. Contributed reagents/materials/ analysis tools: XL. Wrote the paper: XL.
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Issue or Number:10
PubMed Central ID:PMC3480463
Record Number:CaltechAUTHORS:20121203-103239494
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20121203-103239494
Official Citation:Luo XM, Lei MYY (2012) Recombination Activating Gene-2 Regulates CpG-Mediated Interferon-α Production in Mouse Bone Marrow-Derived Plasmacytoid Dendritic Cells. PLoS ONE 7(10): e47952. doi:10.1371/journal.pone.0047952
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:35761
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:03 Dec 2012 19:31
Last Modified:12 Feb 2020 00:24

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