2013
DOI: 10.4049/jimmunol.1300376
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A Synthetic TLR3 Ligand Mitigates Profibrotic Fibroblast Responses by Inducing Autocrine IFN Signaling

Abstract: Activation of Toll-like receptor-3 (TLR3) by exogenous microbial ligands or endogenous injury-associated ligands leads to production of type I interferon (IFN). Scleroderma patients with progressive skin fibrosis display an IFN-regulated gene signature, implicating TLR3 signaling in the disease. We now show that TLR3 expression was detected on foreskin, adult skin and lung fibroblasts, and TLR3 levels were significantly elevated in a subset of scleroderma skin biopsies. In explanted skin and lung fibroblasts, … Show more

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Cited by 51 publications
(37 citation statements)
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“…Responsiveness to PRR ligands is a characteristic feature of fibroblasts throughout the body. Ovarian, skin, lung, intestinal and foreskin fibroblasts respond to poly (I:C) by upregulating the expression of interferon (IFN) β, cytokines and interferon-stimulated genes (ISG) 34,4042 . Our findings indicate that following exposure to poly (I:C), a dsRNA analogue that is a common intermediate in viral replication, FRT fibroblasts upregulate the expression and secretion of ISGs, cytokines and chemokines.…”
Section: Discussionmentioning
confidence: 99%
“…Responsiveness to PRR ligands is a characteristic feature of fibroblasts throughout the body. Ovarian, skin, lung, intestinal and foreskin fibroblasts respond to poly (I:C) by upregulating the expression of interferon (IFN) β, cytokines and interferon-stimulated genes (ISG) 34,4042 . Our findings indicate that following exposure to poly (I:C), a dsRNA analogue that is a common intermediate in viral replication, FRT fibroblasts upregulate the expression and secretion of ISGs, cytokines and chemokines.…”
Section: Discussionmentioning
confidence: 99%
“…Poly(I:C) is a synthetic dsRNA analog and has been regarded as a representative RNA ligand not only for TLR3 but also for the cytosolic RNA helicases, such as retinoic acid-inducible gene 1 (RIG-1) and melanoma differentiation-associated gene 5 (MDA5) and extensively used instead of both exogenous and endogenous RNA ligands in many studies [19,25]. It is very well known that TLR3 is a receptor for dsRNA [4].…”
Section: Discussionmentioning
confidence: 99%
“…It is very well known that TLR3 is a receptor for dsRNA [4]. However, in many different cell types, dsRNA can also be recognized by RIG-1 and MDA5 [19,[25][26]. 15 In certain cases, dsRNA-induced effects can be TLR3-independent.…”
Section: Discussionmentioning
confidence: 99%
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