TY - JOUR
T1 - Cutting edge
T2 - DNA sensing via the STING adaptor in myeloid dendritic cells s tolerogenic responses
AU - Huang, Lei
AU - Li, Lingqian
AU - Lemos, Henrique
AU - Chandler, Phillip R.
AU - Pacholczyk, Gabriela
AU - Baban, Babak
AU - Barber, Glen N.
AU - Hayakawa, Yoshihiro
AU - McGaha, Tracy L.
AU - Ravishankar, Buvana
AU - Munn, David H.
AU - Mellor, Andrew L.
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2013/10/1
Y1 - 2013/10/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1301419
DO - 10.4049/jimmunol.1301419
M3 - Article
C2 - 23986532
AN - SCOPUS:84885169498
SN - 0022-1767
VL - 191
SP - 3509
EP - 3513
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -