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Impact of SLC15A4, TASL and TASL2(Gm6377) deficiency on endolysosomal TLR7 and TLR9 responses

ABSTRACT: Nucleic acid sensing by endolysosomal TLR7-9 results in the induction of antiviral and proinflammatory transcriptional responses. We recently identified TASL as the innate immune adaptor mediating TLR7-9-induced IRF5 activation via the interaction with SLC15A4, but its relevance in primary murine cells remained unexplored. Here we assessed the impact of deficiency in TASL and/or its previously uncharacterized paralogue Gm6377, named here TASL2, on endolysosomal TLR responses in primary bone-marrow-derived pDCs and splenic B cells. Double knockout TASLxTASL2 (TASLDKO) phenocopied the strong impairement observed in cells from SLC15A4-deficient feeble mice, while single TASL or TASL2 deficiency showed partial effect. Altogether, this study demonstrates that the SLC15A4-TASL/TASL2 complex play a critical role for TLR7-9-driven inflammatory responses.

ORGANISM(S): Mus musculus

PROVIDER: GSE267786 | GEO | 2024/11/04

REPOSITORIES: GEO

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Impact of SLC15A4, TASL and TASL2(Gm6377) deficiency on endolysosomal TLR7 and TLR9 responses

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