Beyond receptors and signaling: epigenetic factors in the regulation of innate immunity
Identifieur interne : 000487 ( Ncbi/Merge ); précédent : 000486; suivant : 000488Beyond receptors and signaling: epigenetic factors in the regulation of innate immunity
Auteurs : Stuti Mehta ; Kate L. JeffreySource :
- Immunology and cell biology [ 0818-9641 ] ; 2015.
Abstract
The interaction of innate immune cells with pathogens leads to changes in gene expression that elicit our body’s first line of defense against infection. Although signaling pathways and transcription factors have a central role, it is becoming increasingly clear that epigenetic factors, in the form of DNA or histone modifications, as well as noncoding RNAs, are critical for generating the necessary cell lineage as well as context-specific gene expression in diverse innate immune cell types. Much of the epigenetic landscape is set during cellular differentiation; however, pathogens and other environmental triggers also induce changes in histone modifications that can either promote tolerance or ‘train’ innate immune cells for a more robust antigen-independent secondary response. Here we review the important contribution of epigenetic factors to the initiation, maintenance and training of innate immune responses. In addition, we explore how pathogens have hijacked these mechanisms for their benefit and the potential of small molecules targeting chromatin machinery as a way to boost or subdue the innate immune response in disease.
Url:
DOI: 10.1038/icb.2014.101
PubMed: 25559622
PubMed Central: 4885213
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PMC:4885213Le document en format XML
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<front><div type="abstract" xml:lang="en"><p id="P1">The interaction of innate immune cells with pathogens leads to changes in gene expression that elicit our body’s first line of defense against infection. Although signaling pathways and transcription factors have a central role, it is becoming increasingly clear that epigenetic factors, in the form of DNA or histone modifications, as well as noncoding RNAs, are critical for generating the necessary cell lineage as well as context-specific gene expression in diverse innate immune cell types. Much of the epigenetic landscape is set during cellular differentiation; however, pathogens and other environmental triggers also induce changes in histone modifications that can either promote tolerance or ‘train’ innate immune cells for a more robust antigen-independent secondary response. Here we review the important contribution of epigenetic factors to the initiation, maintenance and training of innate immune responses. In addition, we explore how pathogens have hijacked these mechanisms for their benefit and the potential of small molecules targeting chromatin machinery as a way to boost or subdue the innate immune response in disease.</p>
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<contrib-group><contrib contrib-type="author"><name><surname>Mehta</surname>
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<contrib contrib-type="author"><name><surname>Jeffrey</surname>
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<aff id="A1">Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA</aff>
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<author-notes><corresp id="FN1">Correspondence: Dr KL Jeffrey, Massachusetts General Hospital, Harvard Medical School, 60 Blossom St, Thier340, Boston, MA 02114, USA. <email>KJeffrey@mgh.harvard.edu</email>
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<fn id="FN2" fn-type="conflict"><p><bold>CONFLICT OF INTEREST</bold>
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<p>The authors declare no conflict of interest.</p>
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<pub-date pub-type="nihms-submitted"><day>18</day>
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<abstract><p id="P1">The interaction of innate immune cells with pathogens leads to changes in gene expression that elicit our body’s first line of defense against infection. Although signaling pathways and transcription factors have a central role, it is becoming increasingly clear that epigenetic factors, in the form of DNA or histone modifications, as well as noncoding RNAs, are critical for generating the necessary cell lineage as well as context-specific gene expression in diverse innate immune cell types. Much of the epigenetic landscape is set during cellular differentiation; however, pathogens and other environmental triggers also induce changes in histone modifications that can either promote tolerance or ‘train’ innate immune cells for a more robust antigen-independent secondary response. Here we review the important contribution of epigenetic factors to the initiation, maintenance and training of innate immune responses. In addition, we explore how pathogens have hijacked these mechanisms for their benefit and the potential of small molecules targeting chromatin machinery as a way to boost or subdue the innate immune response in disease.</p>
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