Title SYK signalling in NLRP3 inflammasome‐mediated response of murine microglia activated by immune complexes formed of viral proteins and specific IgG
Authors Mašalaitė, Kristina ; Norkienė, Milda ; Žvirblienė, Aurelija ; Lučiūnaitė, Asta
DOI 10.1002/eji.70199
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Is Part of European journal of immunology.. Weinheim : Wiley-VCH GmbH. 2026, vol. 56, iss. 5, art. no. e70199, p. [1-12].. ISSN 0014-2980. eISSN 1521-4141
Keywords [eng] antigen presentation ; immune complexes ; NLRP3 ; SYK
Abstract [eng] Viral infections might trigger systemic inflammatory responses characterised by inflammasome activation and cytokine release, driven by immune complex (IC) formation, but the precise mechanism remains unknown. The NLRP3 inflammasome is a vital component of innate immunity that plays a significant role in inflammatory responses. The involvement of the non‐receptor spleen tyrosine kinase (SYK) in the activation of the NLRP3 inflammasome has been demonstrated. SYK plays a critical role in signal transduction pathways of immunoreceptors and regulates NLRP3 inflammasome activation. Our previous study showed that viral antigens and their IC with specific antibodies trigger NLRP3 inflammasome activation in macrophages. Therefore, we studied the role of SYK in IC‐induced NLRP3 inflammasome activation pathway using primary mouse microglia as a macrophage model. The inflammasome activation was analysed by measuring cytokine secretion, ASC speck formation, and NLRP3 expression. To link SYK activation to NLRP3 inflammasome activation and other macrophage functional properties, we employed a specific SYK inhibitor, R406. We demonstrated SYK involvement in NLRP3 inflammasome activation by viral IC and in SYK‐dependent antigen presentation in microglia after IC phagocytosis. Our findings also revealed lipid raft clustering upstream of SYK activation. These results may explain the mechanisms behind severe inflammation caused by viral IC.
Published Weinheim : Wiley-VCH GmbH
Type Journal article
Language English
Publication date 2026
CC license CC license description