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Plos Genetics : Interferon Regulatory Factor 8 Regulates Pathways for Antigen Presentation in Myeloid Cells and During Tuberculosis, Volume 7

By Roopenian, Derry C.

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Book Id: WPLBN0003931698
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Reproduction Date: 2015

Title: Plos Genetics : Interferon Regulatory Factor 8 Regulates Pathways for Antigen Presentation in Myeloid Cells and During Tuberculosis, Volume 7  
Author: Roopenian, Derry C.
Volume: Volume 7
Language: English
Subject: Journals, Science, Genetics
Collections: Periodicals: Journal and Magazine Collection (Contemporary), PLoS Genetics
Historic
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Publisher: Plos

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Roopenian, D. C. (n.d.). Plos Genetics : Interferon Regulatory Factor 8 Regulates Pathways for Antigen Presentation in Myeloid Cells and During Tuberculosis, Volume 7. Retrieved from http://worldlibrary.org/


Description
Description : IRF8 (Interferon Regulatory Factor 8) plays an important role in defenses against intracellular pathogens, including several aspects of myeloid cells function. It is required for ontogeny and maturation of macrophages and dendritic cells, for activation of anti-microbial defenses, and for production of the Th1-polarizing cytokine interleukin-12 (IL-12) in response to interferon gamma (IFNc) and protection against infection with Mycobacterium tuberculosis. The transcriptional programs and cellular pathways that are regulated by IRF8 in response to IFNc and that are important for defenses against M. tuberculosis are poorly understood. These were investigated by transcript profiling and chromatin immunoprecipitation on microarrays (ChIP-chip). Studies in primary macrophages identified 368 genes that are regulated by IRF8 in response to IFNc/CpG and that behave as stably segregating expression signatures (eQTLs) in F2 mice fixed for a wild-type or mutant allele at IRF8. A total of 319 IRF8 binding sites were identified on promoters genome-wide (ChIP-chip) in macrophages treated with IFNc/CpG, defining a functional G/AGAAnTGAAA motif. An analysis of the genes bearing a functional IRF8 binding site, and showing regulation by IFNc/CpG in macrophages and/or in M. tuberculosis-infected lungs, revealed a striking enrichment for the pathways of antigen processing and presentation, including multiple structural and enzymatic components of the Class I and Class II MHC (major histocompatibility complex) antigen presentation machinery. Also significantly enriched as IRF8 targets are the group of endomembrane- and phagosome-associated small GTPases of the IRG (immunity-related GTPases) and GBP (guanylate binding proteins) families. These results identify IRF8 as a key regulator of early response pathways in myeloid cells, including phagosome maturation, antigen processing, and antigen presentation by myeloid cells.

 

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