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Review
. 2012 Mar;142(3):223-31.
doi: 10.1016/j.clim.2011.12.007. Epub 2011 Dec 29.

DNA-responsive inflammasomes and their regulators in autoimmunity

Divaker Choubey  1
Affiliations
Review

DNA-responsive inflammasomes and their regulators in autoimmunity

Divaker Choubey. Clin Immunol. 2012 Mar.

Abstract

Upon sensing microbial and self-derived DNA, DNA sensors initiate innate immune responses. These sensors include the interferon (IFN)-inducible Toll-like receptor 9 (TLR9) and PYHIN proteins. Upon sensing DNA, cytosolic (murine Aim2 and human AIM2) and nuclear (IFI16) PYHIN proteins recruit an adaptor protein (ASC) and pro-caspase-1 to form an inflammasome, which activates caspase-1. The activated caspase-1 cleaves pro-IL-1β and pro-IL-18 to generate active forms. However, upon sensing cytosolic DNA, the IFI16 protein recruits STING to induce the expression of type I IFN. Recognition of self DNA by innate immune cells contributes to the production of increased levels of type I IFN. Given that the type I IFNs modulate the expression of inflammasome proteins and that the IFN-inducible proteins inhibit the activity of DNA-responsive inflammasomes, an improved understanding of the molecular mechanisms that regulate the activity of DNA-responsive inflammasomes is likely to identify new therapeutic targets to treat autoimmune diseases.

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Conflict of interest statement

Conflict of interest statement: The author does not have any potential financial conflict of interest related to this manuscript.

Figures

Figure 1
Figure 1
Sensing of self DNA by DNA sensor proteins and induction of innate immune responses by cell of the innate immune system in mouse models of SLE.
Figure 2
Figure 2
Upon sensing DNA, AIM2 and IFI16 proteins activate different innate immune responses.
See this image and copyright information in PMC

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