期刊
NATURE REVIEWS MOLECULAR CELL BIOLOGY
卷 23, 期 4, 页码 286-301出版社
NATURE PORTFOLIO
DOI: 10.1038/s41580-021-00430-1
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资金
- NIH [R35GM142687, 5K12CA215110]
- Rita Allen Foundation
- Yale Cancer Center
DSRNA, whether of viral origin or endogenous, can lead to immune disorders or be utilized for immunotherapy. Organisms have mechanisms to recognize and respond to dsRNA to minimize potential infections, with infected and dysregulated cells both triggering immune responses.
Double-stranded RNAs (dsRNAs) are recognized by designated cellular sensors to mount an immune response. Although dsRNAs are generally of viral origin, dysregulation of several cellular processes can lead to accumulation of endogenous dsRNAs. These self-derived dsRNAs are often associated with immune disorders, but their immunogenicity can also be exploited for immunotherapy. Double-stranded RNA (dsRNA) is associated with most viral infections - it either constitutes the viral genome (in the case of dsRNA viruses) or is generated in host cells during viral replication. Hence, nearly all organisms have the capability of recognizing dsRNA and mounting a response, the primary aim of which is to mitigate the potential infection. In vertebrates, a set of innate immune receptors for dsRNA induce a multitude of cell-intrinsic and cell-extrinsic immune responses upon dsRNA recognition. Notably, recent studies showed that vertebrate cells can accumulate self-derived dsRNAs or dsRNA-like species upon dysregulation of several cellular processes, activating the very same immune pathways as in infected cells. On the one hand, such aberrant immune activation in the absence of infection can lead to pathogenesis of immune disorders, such as Aicardi-Goutieres syndrome. On the other hand, the same innate immune reaction can be induced in a controlled setting for a therapeutic benefit, as occurs in immunotherapies. In this Review, we describe mechanisms by which immunostimulatory dsRNAs are generated in mammalian cells, either by viruses or by the host cells, and how cells respond to them, with the focus on recent developments regarding the role of cellular dsRNAs in immune modulation.
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