Synergistic Stimulation with Different TLR7 Ligands Modulates Gene Expression Patterns in the Human Plasmacytoid Dendritic Cell Line CAL-1

Mediators of Inflammation
Tobias HilbertSven Klaschik

Abstract

TLR7 ligation in plasmacytoid dendritic cells is promising for the treatment of cancer, allergy, and infectious diseases; however, high doses of ligands are required. We hypothesized that the combination of structurally different TLR7 ligands exponentiates the resulting immune response. CAL-1 (human pDC line) cells were incubated with the TLR7-specific adenine analog CL264 and single-stranded 9.2s RNA. Protein secretion was measured by ELISA. Microarray technique was used to detect modified gene expression patterns upon synergistic stimulation, revealing underlying functional groups and networks. Cell surface binding properties were studied using FACS analysis. CL264 in combination with 9.2s RNA significantly enhanced cytokine and interferon secretion to supra-additive levels. This effect was due to a stronger stimulation of already regulated genes (by monostimulation) as well as to recruitment of thus far unregulated genes. Top scoring canonical pathways referred to immune-related processes. Network analysis revealed IL-1β, IL-6, TNF, and IFN-β as major regulatory nodes, while several minor regulatory nodes were also identified. Binding of CL264 to the cell surface was enhanced by 9.2s RNA. Structurally different TLR7 ligands ...Continue Reading

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Citations

May 2, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chun-Feng YuNatalija Novak
May 1, 2019·Cancers·Maria Rosaria SapienzaStefano Pileri
Nov 5, 2019·Frontiers in Immunology·Amanda B MacedoAlberto Bosque
May 1, 2021·International Journal of Molecular Sciences·Dóra BenczeKitti Pázmándi

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Methods Mentioned

BETA
Fluorescent Activated Cell Sorting
FACS
ELISA
Assay
transfection
confocal microscopy

Software Mentioned

IPA
BRB ArrayTools
GraphPad PRISM
FlowJo

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