ArticleJournal of immunology (Baltimore, Md. : 1950)2013
The ataxia telangiectasia mutated kinase pathway regulates IL-23 expression by human dendritic cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Dendritic cells in inborn errors of immunity.Frontiers in immunology · 2023Review
- ATM at the crossroads of reactive oxygen species and autophagy.International journal of biological sciences · 2021Review
- CRL4The Journal of experimental medicine · 2018Article
- Inflammation, a significant player of Ataxia-Telangiectasia pathogenesis?Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018Review
- Biological effects of radiation on cancer cells.Military Medical Research · 2018Review
- IRE1α Implications in Endoplasmic Reticulum Stress-Mediated Development and Pathogenesis of Autoimmune Diseases.Frontiers in immunology · 2018Review
- The TAM family as a therapeutic target in combination with radiation therapy.Emerging topics in life sciences · 2017Article
- Endoplasmic Reticulum Stress Sensor IRE1α Enhances IL-23 Expression by Human Dendritic Cells.Frontiers in immunology · 2017Article
- Stromal fibroblasts support dendritic cells to maintain IL-23/Th17 responses after exposure to ionizing radiation.Journal of leukocyte biology · 2016Article
- Ataxia Telangiectasia Mutated Dysregulation Results in Diabetic Retinopathy.Stem cells (Dayton, Ohio) · 2016Article
- Article
- CDKN1A regulates Langerhans cell survival and promotes Treg cell generation upon exposure to ionizing irradiation.Nature immunology · 2015Article
- Identification of a non-growth factor role for GM-CSF in advanced atherosclerosis: promotion of macrophage apoptosis and plaque necrosis through IL-23 signaling.Circulation research · 2015Article
- The unfolded protein response and the phosphorylations of activating transcription factor 2 in the trans-activation of il23a promoter produced by β-glucans.The Journal of biological chemistry · 2014Article
- Novel function for the p38-MK2 signaling pathway in circulating CD1c+ (BDCA-1+) myeloid dendritic cells from healthy donors and advanced cancer patients; inhibition of p38 enhances IL-12 whilst suppressing IL-10.International journal of cancer · 2014Article
- Bacterial amyloid curli activates the host unfolded protein response via IRE1α in the presence of HLA-B27.Gut microbesArticle
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Authors and funding
12 authors at 2 institutions in 2 countries.
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Abstract
Little is known of the regulation of IL-23 secretion in dendritic cells (DC) despite its importance for human Th17 responses. In this study, we show for first time, to our knowledge, that the ataxia telangiectasia mutated (ATM) pathway, involved in DNA damage sensing, acts as an IL-23 repressor. Inhibition of ATM with the highly selective antagonist KU55933 markedly increased IL-23 secretion in human monocyte-derived DC and freshly isolated myeloid DC. In contrast, inhibiting the closely related mammalian target of rapamycin had no effect on IL-23. Priming naive CD4(+) T cells with ATM-inhibited DC increased Th17 responses over and above those obtained with mature DC. Although ATM blockade increased the abundance of p19, p35, and p40 mRNA, IL-12p70 secretion was unaffected. To further examine a role for ATM in IL-23 regulation, we exposed DC to low doses of ionizing radiation. Exposure of DC to x-rays resulted in ATM phosphorylation and a corresponding depression of IL-23. Importantly, ATM inhibition with KU55933 prevented radiation-induced ATM phosphorylation and abrogated the capacity of x-rays to suppress IL-23. To explore how ATM repressed IL-23, we examined a role for endoplasmic reticulum stress responses by measuring generation of the spliced form of X-box protein-1, a key endoplasmic reticulum stress transcription factor. Inhibition of ATM increased the abundance of X-box protein-1 mRNA, and this was followed 3 h later by increased peak p19 transcription and IL-23 release. In summary, ATM activation or inhibition, respectively, inhibited or augmented IL-23 release. This novel role of the ATM pathway represents a new therapeutic target in autoimmunity and vaccine development.
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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.