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Current Rheumatology Reports
Published in: Current Rheumatology Reports 1/2015

01-01-2015 | Scleroderma (J Varga, Section Editor)

Emerging Roles of Innate Immune Signaling and Toll-Like Receptors in Fibrosis and Systemic Sclerosis

Authors: Swati Bhattacharyya, John Varga

Published in: Current Rheumatology Reports | Issue 1/2015

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Abstract

Pathological fibrosis is a distinguishing hallmark of systemic sclerosis (SSc) as well as a number of more common conditions. Fibrosis is a complex and dynamic process associated with immune dysregulation, vasculopathy, and uncontrolled extracellular matrix production leading to intractable scar formation in the skin and internal organs. Persistent or recurrent chemical, infectious, mechanical, or autoimmune injury in genetically predisposed individuals causes sustained fibroblasts activation. Innate immune signaling via toll-like receptors (TLRs) is increasingly recognized as a key player driving the persistent fibrotic response in SSc. In particular, expression of TLR4 as well as its endogenous ligands are elevated in lesional tissue from patients with SSc. Ligand-induced TLR4 activation elicits potent stimulatory effects on fibrotic gene expression and myofibroblast differentiation. Furthermore, TLR4 appears to sensitize fibroblasts to the profibrotic stimulatory effect of transforming growth factor-β. This review highlights recent advances and emerging paradigms for understanding the regulation, complex functional roles, and therapeutic potential of TLRs in SSc pathogenesis.
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Metadata
Title
Emerging Roles of Innate Immune Signaling and Toll-Like Receptors in Fibrosis and Systemic Sclerosis
Authors
Swati Bhattacharyya
John Varga
Publication date
01-01-2015
Publisher
Springer US
Published in
Current Rheumatology Reports / Issue 1/2015
Print ISSN: 1523-3774
Electronic ISSN: 1534-6307
DOI
https://doi.org/10.1007/s11926-014-0474-z

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