PMID- 33540529 OWN - NLM STAT- PubMed-not-MEDLINE VI - 10 IP - 3 TI - Making Sense of Intracellular Nucleic Acid Sensing in Type I Interferon Activation in Sjögren's Syndrome. LA - eng PT - Journal Article PT - Review PL - Switzerland TA - J Clin Med JT - Journal of clinical medicine JID - 101606588 IS - 2077-0383 (Print) LID - 532 [pii] LID - 10.3390/jcm10030532 [doi] FAU - Huijser, Erika AU - Huijser E AD - Department of Immunology, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands. FAU - Versnel, Marjan A AU - Versnel MA AD - Department of Immunology, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands. IS - 2077-0383 (Linking) OTO - NOTNLM OT - Sjögren’s syndrome OT - autoimmune OT - cytosolic pattern recognition receptors OT - interferon OT - nucleic acid sensors PMC - PMC7867173 LR - 20210210 DP - 2021 Feb 02 DEP - 20210202 AB - Primary Sjögren's syndrome (pSS) is a systemic autoimmune rheumatic disease characterized by dryness of the eyes and mucous membranes, which can be accompanied by various extraglandular autoimmune manifestations. The majority of patients exhibit persistent systemic activation of the type I interferon (IFN) system, a feature that is shared with other systemic autoimmune diseases. Type I IFNs are integral to anti-viral immunity and are produced in response to stimulation of pattern recognition receptors, among which nucleic acid (NA) receptors. Dysregulated detection of endogenous NAs has been widely implicated in the pathogenesis of systemic autoimmune diseases. Stimulation of endosomal Toll-like receptors by NA-containing immune complexes are considered to contribute to the systemic type I IFN activation. Accumulating evidence suggest additional roles for cytosolic NA-sensing pathways in the pathogenesis of systemic autoimmune rheumatic diseases. In this review, we will provide an overview of the functions and signaling of intracellular RNA- and DNA-sensing receptors and summarize the evidence for a potential role of these receptors in the pathogenesis of pSS and the sustained systemic type I IFN activation.