Tumor Progression Locus 2 Promotes Mouse Plasmacytoid Dendritic Cell Cytokine Secretion and Signaling

نویسندگان

چکیده

Abstract The autoimmune disorder systemic lupus erythematosus is thought to be caused by the inefficient clearance of dying cells. This releases nucleic acid debris that stimulates type I interferon (T1 IFN) secretion. Plasmacytoid dendritic cells (pDCs) are major source T1 IFNs, which causally linked pathogenesis. Both IFNs and pDCs thus focus intense studies for immunotherapies. serine-threonine kinase, tumor progression locus 2 (TPL2), negatively regulates IFN secretion conventional (cDCs) macrophages in response Toll-like receptor 9 (TLR9) stimulation vitro. In contrast, we others have shown TPL2 required production TLR9-stimulated pDCs. goal this study validate TPL2-dependent regulation pDC function vivoand delineate mechanisms responsible. cDCs develop normally Tpl2−/−mice, but Tpl2−/−mice show defective proinflammatory cytokines administration CpG or R848 (TLR7) vivo. same defect cytokine was observed bone marrow-derived A modest TLR-induced expression maturation markers CD80, CD86 MHC class II seen Tpl2−/−pDCs, suggesting impaired NFkB activation. Flow cytometric measurement phosphoproteins demonstrated also activation MAPK ribosomal S6 kinase pathways Ongoing examining role TLR trafficking These data establish functions, may exploited therapeutic intervention other IFN-related diseases. Supported grants from NIH/NIAMS (R21 AR075317) titled "Tpl2 SLE pathogenesis"

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ژورنال

عنوان ژورنال: Journal of Immunology

سال: 2023

ISSN: ['1550-6606', '0022-1767']

DOI: https://doi.org/10.4049/jimmunol.210.supp.167.07