ArticleDiabetes2011
Interleukin-1β produced in response to islet autoantigen presentation differentiates T-helper 17 cells at the expense of regulatory T-cells: Implications for the timing of tolerizing immunotherapy.
Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- Trial
- IL-17F induces inflammation, dysfunction and cell death in mouse islets.Scientific reports · 2020Article
- FuFangChangTai Decoction Activates Macrophages via Inducing Autophagy.Evidence-based complementary and alternative medicine : eCAM · 2019Article
- CD122 blockade restores immunological tolerance in autoimmune type 1 diabetes via multiple mechanisms.JCI insight · 2018Article
- APC-targeted proinsulin expression inactivates insulin-specific memory CD8Immunology and cell biology · 2017Article
- Expression profiling pre-diabetic mice to uncover drugs with clinical application to type 1 diabetes.Clinical & translational immunology · 2015Article
- Immune protective effect of human alpha-1-antitrypsin gene during β cell transplantation in diabetic mice.Immunologic research · 2015Article
- Th17 Cells in Type 1 Diabetes: Role in the Pathogenesis and Regulation by Gut Microbiome.Mediators of inflammation · 2015Review
- Combination therapy with an anti-IL-1β antibody and GAD65 DNA vaccine can reverse recent-onset diabetes in the RIP-GP mouse model.Diabetes · 2014Article
- CD8+ dendritic cell-mediated tolerance of autoreactive CD4+ T cells is deficient in NOD mice and can be corrected by blocking CD40L.Journal of leukocyte biology · 2014Article
- Article
- Article
- P2X7 blockade attenuates murine lupus nephritis by inhibiting activation of the NLRP3/ASC/caspase 1 pathway.Arthritis and rheumatism · 2013Article
- Double deficiency in IL-17 and IFN-γ signalling significantly suppresses the development of diabetes in the NOD mouse.Diabetologia · 2013Article
- Innate immunity and resistance to tolerogenesis in allotransplantation.Frontiers in immunology · 2012Article
- Synergistic reversal of type 1 diabetes in NOD mice with anti-CD3 and interleukin-1 blockade: evidence of improved immune regulation.Diabetes · 2012Article
- CD4 T cells and their antigens in the pathogenesis of autoimmune diabetes.Current opinion in immunology · 2011Review
- Current status of immunomodulatory and cellular therapies in preclinical and clinical islet transplantation.Journal of transplantation · 2011Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe effectiveness of tolerizing immunotherapeutic strategies, such as anti-CD40L or dendritic cells (DCs), is greater when administered to young nonobese diabetic (NOD) mice than at peak insulitis. RelB(lo) DCs, generated in the presence of an nuclear factor-κB inhibitor, induce T-regulatory (Treg) cells and suppress inflammation in a model of rheumatoid arthritis. Interleukin (IL)-1β is overexpressed in humans and mice at risk of type 1 diabetes, dysregulates Treg cells, and accelerates diabetes in NOD mice. We investigated the relationship between IL-1β production and the response to RelB(lo) DCs in the prediabetic period. RESEARCH DESIGN AND
methodsWe injected RelB(lo) DCs subcutaneously into 4- or 14-week-old NOD mice and tracked the incidence of diabetes and effect on Treg cell function. We measured the expression of proinflammatory cytokines by stimulated splenocytes and unstimulated islets from mice of different ages and strains and proliferative and cytokine responses of T effectors to Treg in vitro.
resultsTolerizing RelB(lo) DCs significantly inhibited diabetes progression when administered to 4-week-old but not 14-week-old mice. IL-1β production by NOD splenocytes and mRNA expression by islets increased from 6 to 16 weeks of age when major histocompatibility complex (MHC)-restricted islet antigen presentation to autoreactive T-cells occurred. IL-1 reduced the capacity of Treg cells to suppress effector cells and promoted their conversion to Th17 cells. RelB(lo) DCs exacerbated the IL-1-dependent decline in Treg function and promoted Th17 conversion.
conclusionsIL-1β, generated by islet-autoreactive cells in MHC-susceptible mice, accelerates diabetes by differentiating Th17 at the expense of Treg. Tolerizing DC therapies can regulate islet autoantigen priming and prevent diabetes, but progression past the IL-1β/IL-17 checkpoint signals the need for other strategies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.