Hyperresponsive cytosolic DNA-sensing pathway in monocytes from primary Sjögren’s syndrome
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Le résumé fourni par la source
OBJECTIVES: Cytosolic DNA-sensing pathway stimulation prompts type I IFN (IFN-I) production, but its role in systemic IFN-I pathway activation in primary SS (pSS) is poorly studied. Here we investigate the responsiveness of pSS monocytes and plasmacytoid dendritic cells (pDCs) to stimulator of interferon genes (STING) activation in relation to systemic IFN-I pathway activation and compare this with SLE. METHODS: Expression of DNA-sensing receptors cGAS, IFI16, ZBP-1 and DDX41, signalling molecules STING, TBK1 and IRF3, positive and negative STING regulators, and IFN-I-stimulated genes MxA, IFI44, IFI44L, IFIT1 and IFIT3 was analysed in whole blood, CD14+ monocytes, pDCs, and salivary glands by RT-PCR, monocyte RNA sequencing data, flow cytometry and immunohistochemical staining. Peripheral blood mononuclear cells (PBMCs) from pSS, SLE and healthy controls (HCs) were stimulated with STING agonist 2'3'-cGAMP. STING phosphorylation (pSTING) and intracellular IFNα were evaluated using flow cytometry. RESULTS: STING activation induced a significantly higher proportion of IFNα-producing monocytes, but not pDCs, in both IFN-low and IFN-high pSS compared with HC PBMCs. Additionally, a trend towards more pSTING+ monocytes was observed in pSS and SLE, most pronounced in IFN-high patients. Positive STING regulators TRIM38, TRIM56, USP18 and SENP7 were significantly higher expression in pSS than HC monocytes, while the dual-function STING regulator RNF26 was downregulated in pSS monocytes. STING was expressed in mononuclear infiltrates and ductal epithelium in pSS salivary glands. STING stimulation induced pSTING and IFNα in pSS and SLE pDCs. CONCLUSION: pSS monocytes and pDCs are hyperresponsive to stimulation of the STING pathway, which was not restricted to patients with IFN-I pathway activation.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Hyperresponsive cytosolic DNA-sensing pathway in monocytes from primary Sjögren’s syndrome
- Date Crossref
- 12/01/2022
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Erasmus MC pays non établi dans la noticeÉtablissement de santé
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Erasmus MC Cancer Institute pays non établi dans la noticeÉtablissement de santé
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Utrecht University pays non établi dans la noticeUniversité ou école supérieure
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University Medical Center Utrecht Erasmus MC Cancer Institute pays non établi dans la noticeÉtablissement de santé
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Department of Immunology pays non établi dans la noticeInstitution
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Department of Pathology pays non établi dans la noticeInstitution
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University Medical Centre Utrecht Center for Translational Immunology pays non établi dans la noticeUniversité ou école supérieure
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Department of Rheumatology and Clinical Immunology pays non établi dans la noticeÉtablissement de santé
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Division of Allergy and Clinical Immunology Department of Internal Medicine pays non établi dans la noticeÉtablissement de santé
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University Medical Center Rotterdam Laboratory Medical Immunology pays non établi dans la noticeUniversité ou école supérieure
Erasmus MC, Erasmus MC Cancer Institute et Utrecht University, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.