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Cutting Edge: DNA Sensing via the STING Adaptor in Myeloid Dendritic Cells Induces Potent Tolerogenic Responses

Lookup NU author(s): Dr Lei HuangORCiD, Dr Henrique De Paula LemosORCiD, Emeritus Professor Andrew MellorORCiD

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Abstract

Cytosolic DNA sensing via the stimulator of IFN genes (STING) adaptor incites autoimmunity by inducing type I IFN (IFN-αβ). In this study, we show that DNA is also sensed via STING to suppress immunity by inducing IDO. STING gene ablation abolished IFN-αβ and IDO induction by dendritic cells (DCs) after DNA nanoparticle (DNP) treatment. Marginal zone macrophages, some DCs, and myeloid cells ingested DNPs, but CD11b(+) DCs were the only cells to express IFN-β, whereas CD11b(+) non-DCs were major IL-1β producers. STING ablation also abolished DNP-induced regulatory responses by DCs and regulatory T cells, and hallmark regulatory responses to apoptotic cells were also abrogated. Moreover, systemic cyclic diguanylate monophosphate treatment to activate STING induced selective IFN-β expression by CD11b(+) DCs and suppressed Th1 responses to immunization. Thus, previously unrecognized functional diversity among physiologic innate immune cells regarding DNA sensing via STING is pivotal in driving immune responses to DNA.

Publication metadata

Author(s): Huang L, Li L, Lemos H, Chandler PR, Pacholczyk G, Baban B, Barber GN, Hayakawa Y, McGaha TL, Ravishankar B, Munn DH, Mellor AL

Publication type: Article

Publication status: Published

Journal: The Journal of Immunology

Year: 2013

Volume: 191

Issue: 7

Pages: 3509-3513

Print publication date: 01/10/2013

Online publication date: 28/08/2013

ISSN (print): 0022-1767

ISSN (electronic): 1550-6606

Publisher: American Association of Immunologists

URL: http://doi.org/10.4049/jimmunol.1301419

DOI: 10.4049/jimmunol.1301419

PubMed id: 23986532

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