Cytosolic DNA sensing via the stimulator of interferon genes adaptor: Yin and Yang of immune responses to DNA

Henrique Lemos, Lei Huang, Tracy L. Mcgaha, Andrew L. Mellor

Research output: Contribution to journalReview article

19 Citations (Scopus)

Abstract

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-β) release, a potent immune activator. DNA sensing to induce IFN-β triggers host immunity to pathogens but constitutive DNA sensing can induce sustained IFN-β release that incites autoimmunity. Here, we focus on cytosolic DNA sensing via the STING/IFN-β pathway that regulates immune responses. Recent studies reveal that cytosolic DNA sensing via the STING/IFN-β 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.

Original languageEnglish (US)
Pages (from-to)2847-2853
Number of pages7
JournalEuropean Journal of Immunology
Volume44
Issue number10
DOIs
StatePublished - Oct 1 2014

Fingerprint

Yin-Yang
Interferons
DNA
Genes
Regulatory T-Lymphocytes
Autoimmunity
Immunity
Indoleamine-Pyrrole 2,3,-Dioxygenase
Interferon Type I
Helper-Inducer T-Lymphocytes
Tryptophan
Disease Progression

Keywords

  • Autoimmunity
  • DNA sensors
  • STING
  • Tolerance
  • Type I Interferon

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Cytosolic DNA sensing via the stimulator of interferon genes adaptor : Yin and Yang of immune responses to DNA. / Lemos, Henrique; Huang, Lei; Mcgaha, Tracy L.; Mellor, Andrew L.

In: European Journal of Immunology, Vol. 44, No. 10, 01.10.2014, p. 2847-2853.

Research output: Contribution to journalReview article

Lemos, Henrique ; Huang, Lei ; Mcgaha, Tracy L. ; Mellor, Andrew L. / Cytosolic DNA sensing via the stimulator of interferon genes adaptor : Yin and Yang of immune responses to DNA. In: European Journal of Immunology. 2014 ; Vol. 44, No. 10. pp. 2847-2853.
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