In:
The Journal of Immunology, The American Association of Immunologists, Vol. 192, No. 12 ( 2014-06-15), p. 5993-5997
Abstract:
Cytosolic detection of DNA is crucial for the initiation of antiviral immunity but can also cause autoimmunity in the context of endogenous nucleic acids being sensed. Mutations in the human 3′ repair exonuclease 1 (TREX1) have been linked to the type I IFN–associated autoimmune disease Aicardi–Goutières syndrome. The exact mechanisms driving unabated type I IFN responses in the absence of TREX1 are only partly understood, but it appears likely that accumulation of endogenous DNA species triggers a cell-autonomous immune response by activating a cytosolic DNA receptor. In this article, we demonstrate that knocking out the DNA sensor cyclic GMP–AMP synthase completely abrogates spontaneous induction of IFN-stimulated genes in TREX1-deficient cells. These findings indicate a key role of cyclic GMP–AMP synthase for the initiation of self-DNA–induced autoimmune disorders, thus providing important implications for novel therapeutic approaches.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.1400737
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2014
detail.hit.zdb_id:
1475085-5
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