Browse by author
Lookup NU author(s): Dr Henrique De Paula LemosORCiD, Dr Lei HuangORCiD, Dr Rong Ou, Emeritus Professor Andrew MellorORCiD
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Reagents that activate the signaling adaptor Stimulator of Interferon Genes (STING) suppress experimentally induced autoimmunity in murine models of multiple sclerosis and arthritis. In this study, we evaluated STING agonists as potential reagents to inhibit spontaneous autoimmune Type I Diabetes (T1D) onset in NOD female mice. Treatments with DNA nanoparticles (DNPs), which activate STING when cargo DNA is sensed, delayed T1D onset and reduced T1D incidence when administered before T1D onset. DNP treatment elevated indoleamine 2,3 dioxygenase (IDO) activity, which regulates T cell immunity, in spleen, pancreatic lymph nodes and pancreas of NOD mice. Therapeutic responses to DNPs were partially reversed by inhibiting IDO and DNP treatment synergized with insulin therapy to further delay T1D onset and reduce T1D incidence. Treating pre-diabetic NOD mice with cyclic guanyl-adenyl dinucleotide (cGAMP) to activate STING directly delayed T1D onset and stimulated IFN, while treatment with cyclic diguanyl nucleotide (cdiGMP) did not delay T1D onset or induce IFN in NOD mice. DNA sequence analyses revealed that NOD mice possess a STING polymorphism that may explain differential responses to cGAMP and cdiGMP. In summary, STING agonists attenuate T1D progression and DNPs enhance therapeutic responses to insulin therapy. Accepted
Author(s): Lemos H, Mohamed E, Huang L, Chandler PR, Ou R, Pacholczyk R, Mellor AL
Publication type: Article
Publication status: Published
Journal: Immunology
Year: 2019
Volume: 158
Issue: 4
Pages: 353-361
Print publication date: 15/11/2019
Online publication date: 26/09/2019
Acceptance date: 16/09/2019
ISSN (print): 0019-2805
ISSN (electronic): 1365-2567
Publisher: Wiley-Blackwell Publishing Ltd.
URL: https://doi.org/10.1111/imm.13122
DOI: 10.1111/imm.13122
PubMed id: 31557322
Altmetrics provided by Altmetric
