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The role of STING in T lymphocytes (IRM5P.643)

Title: The role of STING in T lymphocytes (IRM5P.643)
Authors: Poltorak, Alexander; Larkin, Bridget; Surpris, Guy; Ilyuha, Vladimir
Source: The Journal of Immunology ; volume 194, issue 1_Supplement, page 59.8-59.8 ; ISSN 0022-1767 1550-6606
Publisher Information: Oxford University Press (OUP)
Publication Year: 2015
Description: The cytoplasmic protein Stimulator of Interferon Genes (STING) plays an essential role in sensing intracellular pathogens and initiating type I IFN responses in myeloid cells. STING detects the presence of cytoplasmic DNA presented by various DNA-binding proteins (e.g. IFI16, DDX41, DAI, RNA Pol III); it also directly binds cyclic dinucleotides produced by intracellular bacteria or by the DNA-binding cyclic GAMP synthase (c-GAS). Once activated, STING phosphorylates TBK1 and IRF3 to trigger type I IFN production. To date STING has only been studied in macrophages and dendritic cells, but early reports showed expression of STING in a variety of tissues including the thymus and spleen, prompting us to ask whether STING might have a functional role in T cells, which account for the majority of cells in the thymus and a larger proportion of cells in the spleen than macrophages and dendritic cells. Here, we show that STING can be activated in T cells by the small molecule DMXAA, resulting in IFNβ production and increased expression of numerous interferon stimulated genes (ISG)—the first evidence to our knowledge of type I IFN production by T cells. Furthermore, RNA-sequencing data revealed unanticipated differences between unstimulated wild type and STING-/- T cells, with STING -/- T cells exhibiting increased expression of genes associated with cytotoxic T lymphocytes, indicating that STING-mediated signaling in T cells may regulate the development of particular T cell subsets.
Document Type: article in journal/newspaper
Language: English
DOI: 10.4049/jimmunol.194.supp.59.8
Availability: https://doi.org/10.4049/jimmunol.194.supp.59.8; https://academic.oup.com/jimmunol/article/194/1_Supplement/59.8/7970256
Rights: https://academic.oup.com/pages/standard-publication-reuse-rights
Accession Number: edsbas.CD8B8A0D
Database: BASE