RGD Reference Report - Activation of target-tissue immune-recognition molecules by double-stranded polynucleotides. - Rat Genome Database

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Activation of target-tissue immune-recognition molecules by double-stranded polynucleotides.

Authors: Suzuki, K  Mori, A  Ishii, KJ  Saito, J  Singer, DS  Klinman, DM  Krause, PR  Kohn, LD 
Citation: Suzuki K, etal., Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2285-90.
RGD ID: 7242894
Pubmed: PMID:10051633   (View Abstract at PubMed)
PMCID: PMC26775   (View Article at PubMed Central)

Abnormal expression of major histocompatibility complex (MHC) class I and class II in various tissues is associated with autoimmune disease. Autoimmune responses can be triggered by viral infections or tissue injuries. We show that the ability of a virus or a tissue injury to increase MHC gene expression is duplicated by any fragment of double-stranded (ds) DNA or dsRNA introduced into the cytoplasm of nonimmune cells. Activation is sequence-independent, is induced by ds polynucleotides as small as 25 bp in length, and is not duplicated by single-stranded polynucleotides. In addition to causing abnormal MHC expression, the ds nucleic acids increase the expression of genes necessary for antigen processing and presentation: proteasome proteins (e.g., LMP2), transporters of antigen peptides; invariant chain, HLA-DM, and the costimulatory molecule B7.1. The mechanism is different from and additive to that of gamma-interferon (gammaIFN), i.e., ds polynucleotides increase class I much more than class II, whereas gammaIFN increases class II more than class I. The ds nucleic acids also induce or activate Stat1, Stat3, mitogen-activated protein kinase, NF-kappaB, the class II transactivator, RFX5, and the IFN regulatory factor 1 differently from gammaIFN. CpG residues are not responsible for this effect, and the action of the ds polynucleotides could be shown in a variety of cell types in addition to thyrocytes. We suggest that this phenomenon is a plausible mechanism that might explain how viral infection of tissues or tissue injury triggers autoimmune disease; it is potentially relevant to host immune responses induced during gene therapy.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to electrical stimulus  IEP 7242894; 7242894 RGD 
cellular response to exogenous dsRNA  IEP 7242894 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ciita  (class II, major histocompatibility complex, transactivator)
Psmb9  (proteasome 20S subunit beta 9)


Additional Information