TLR Stimulation Produces IFN-β as the Primary Driver of IFN Signaling in Nonlymphoid Primary Human Cells
Several human autoimmune diseases are characterized by increased expression of type 1 IFN-stimulated genes in both the peripheral blood and tissue. The contributions of different type I IFNs to this gene signature are uncertain as the type I IFN family consists of 13 alphas and one each of β, ε, κ,...
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Published in | ImmunoHorizons Vol. 4; no. 6; pp. 332 - 338 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
18.06.2020
|
Online Access | Get full text |
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Summary: | Several human autoimmune diseases are characterized by increased expression of type 1 IFN-stimulated genes in both the peripheral blood and tissue. The contributions of different type I IFNs to this gene signature are uncertain as the type I IFN family consists of 13 alphas and one each of β, ε, κ, and ω subtypes. We sought to investigate the contribution of various IFNs to IFN signaling in primary human cell types. We stimulated primary skin, muscle, kidney, and PBMCs from normal healthy human donors with various TLR ligands and measured the expression of type I IFN subtypes and activation of downstream signaling by quantitative PCR. We show that
is the dominant type I IFN expressed upon TLR3 and TLR4 stimulation, and its expression profile is associated with subsequent
transcription. Furthermore, using an IFN-β-specific neutralizing Ab, we show that
expression is inhibited in a dose-dependent manner, suggesting that IFN-β is the primary driver of IFN-stimulated genes following TLR3 and TLR4 engagement. Stimulation with TLR7/8 and TLR9 ligands induced
and
subtypes and
expression only in PBMCs and not in tissue resident cell types. Concordantly, IFN-β neutralization had no effect on
expression in PBMCs potentially because of the combination of
and
expression. Combined, these data highlight the potential role for IFN-β in driving local inflammatory responses in clinically relevant human tissue types and opportunities to treat local inflammation by targeting IFN-β. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2573-7732 2573-7732 |
DOI: | 10.4049/immunohorizons.1800054 |