USP5 negatively regulates the activation of NLRP3 inflammasomes and participates in the pathological and physiological processes of Sjogren's syndrome

• Published in: International immunopharmacology 2024-06, Vol.135, p.112274, Article 112274
• Main Authors: He, Jing, Chen, Yueyue, Xu, Meimei, Wu, Suling
• Format: Article
• Language: English
• Subjects: Animals; Endopeptidases - genetics; Endopeptidases - metabolism; Female; Humans; Inflammasomes - metabolism; Male; Mice; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3; SaB; Signal Transduction; Sjogren's Syndrome - immunology; Sjogren's Syndrome - metabolism; Sjogren's Syndrome - pathology; Submandibular Gland - metabolism; Submandibular Gland - pathology; Ubiquitin-Specific Proteases - genetics; Ubiquitin-Specific Proteases - metabolism; Ubiquitination; USP5
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2024.112274

•USP5 was significantly downregulated in submandibular gland tissue of SS.•USP5 is a negative regulator of NLRP3 via ubiquitination NLRP3.•SalvianolicacidB (SaB), a natural USP5 agonist, can alleviate ss by regulating the USP5/NLRP3 signaling pathway. The current treatment and mechanism of Sjogren's syndrome (SS) are unclear. The purpose of the present study was to potential molecular mechanisms of SS. Immunohistochemical and immunofluorescence techniques reveal the targets and therapeutic approaches of SS. We found through molecular biology techniques such as immunoblotting and immunoprecipitation that USP5 is a novel regulator of NLRP3 involvement in the pathological process of SS. USP5 was significantly downregulated in submandibular gland tissue of SS. Meanwhile, it was found that USP5 is a negative regulator of NLRP3 via ubiquitination NLRP3. In addition, SalvianolicacidB (SaB), a natural USP5 agonist, can alleviate ss by regulating the USP5/NLRP3 signaling pathway. Therefore, this study provides a new mechanism for SS and also provides new therapeutic targets for treating SS.