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2014 ; 44
(10
): 2847-53
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Cytosolic DNA sensing via the stimulator of interferon genes adaptor: Yin and
Yang of immune responses to DNA
#MMPMID25143264
Lemos H
; Huang L
; McGaha TL
; Mellor AL
Eur J Immunol
2014[Oct]; 44
(10
): 2847-53
PMID25143264
show ga
DNA is immunogenic and many cells express cytosolic DNA sensors that activate the
stimulator of interferon genes (STING) adaptor to trigger interferon type I
(IFN-?) release, a potent immune activator. DNA sensing to induce IFN-? triggers
host immunity to pathogens but constitutive DNA sensing can induce sustained
IFN-? release that incites autoimmunity. Here, we focus on cytosolic DNA sensing
via the STING/IFN-? pathway that regulates immune responses. Recent studies
reveal that cytosolic DNA sensing via the STING/IFN-? pathway induces indoleamine
2,3 dioxygenase (IDO), which catabolizes tryptophan to suppress effector and
helper T-cell responses and activate Foxp3-lineage CD4(+) regulatory T (Treg)
cells. During homeostasis, and in some inflammatory settings, specialized innate
immune cells in the spleen and lymph nodes may ingest and sense cytosolic DNA to
reinforce tolerance that prevents autoimmunity. However, malignancies and
pathogens may exploit DNA-induced regulatory responses to suppress natural and
vaccine-induced immunity to malignant and infected cells. In this review, we
discuss the biologic significance of regulatory responses to DNA and novel
approaches to exploit DNA-induced immune responses for therapeutic benefit. The
ability of DNA to drive tolerogenic or immunogenic responses highlights the need
to evaluate immune responses to DNA in physiologic settings relevant to disease
progression or therapy.
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