Targeting TLRs and the inflammasome in systemic sclerosis

John Henderson, Swati Bhattacharyya, John Varga, Steven O'Reilly*

*Corresponding author for this work

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

Systemic sclerosis (SSc) is an idiopathic autoimmune disease characterised by inflammation, vascular problems, cytokine dysregulation and ultimately fibrosis, which accounts for poor prognosis and eventual mortality. At present no curative treatments exist, hence there is an urgent need to better understand the aetiology and develop improved therapies accordingly. Although still widely debated, significant evidence points to upregulation of the innate immune response via the activity of Toll-like receptors (TLRs) and the NLRP3 inflammasome as the start points in a cascade of signaling events which drives excessive extracellular matrix protein production, causing fibrosis. Herein the recent breakthroughs which have implicated TLR signaling and the NLRP3 inflammasome in SSc and the novel therapeutic possibilities this introduces to the field will be discussed.

Original languageEnglish (US)
Pages (from-to)163-169
Number of pages7
JournalPharmacology and Therapeutics
Volume192
DOIs
StatePublished - Dec 1 2018

Fingerprint

Inflammasomes
Systemic Scleroderma
Toll-Like Receptors
Fibrosis
Extracellular Matrix Proteins
Innate Immunity
Autoimmune Diseases
Blood Vessels
Up-Regulation
Cytokines
Inflammation
Mortality
Therapeutics

Keywords

  • Autoimmunity
  • Fibrosis
  • NLRP3 inflammasome
  • Systemic sclerosis
  • Toll-like receptors

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

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title = "Targeting TLRs and the inflammasome in systemic sclerosis",
abstract = "Systemic sclerosis (SSc) is an idiopathic autoimmune disease characterised by inflammation, vascular problems, cytokine dysregulation and ultimately fibrosis, which accounts for poor prognosis and eventual mortality. At present no curative treatments exist, hence there is an urgent need to better understand the aetiology and develop improved therapies accordingly. Although still widely debated, significant evidence points to upregulation of the innate immune response via the activity of Toll-like receptors (TLRs) and the NLRP3 inflammasome as the start points in a cascade of signaling events which drives excessive extracellular matrix protein production, causing fibrosis. Herein the recent breakthroughs which have implicated TLR signaling and the NLRP3 inflammasome in SSc and the novel therapeutic possibilities this introduces to the field will be discussed.",
keywords = "Autoimmunity, Fibrosis, NLRP3 inflammasome, Systemic sclerosis, Toll-like receptors",
author = "John Henderson and Swati Bhattacharyya and John Varga and Steven O'Reilly",
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Targeting TLRs and the inflammasome in systemic sclerosis. / Henderson, John; Bhattacharyya, Swati; Varga, John; O'Reilly, Steven.

In: Pharmacology and Therapeutics, Vol. 192, 01.12.2018, p. 163-169.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Targeting TLRs and the inflammasome in systemic sclerosis

AU - Henderson, John

AU - Bhattacharyya, Swati

AU - Varga, John

AU - O'Reilly, Steven

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Systemic sclerosis (SSc) is an idiopathic autoimmune disease characterised by inflammation, vascular problems, cytokine dysregulation and ultimately fibrosis, which accounts for poor prognosis and eventual mortality. At present no curative treatments exist, hence there is an urgent need to better understand the aetiology and develop improved therapies accordingly. Although still widely debated, significant evidence points to upregulation of the innate immune response via the activity of Toll-like receptors (TLRs) and the NLRP3 inflammasome as the start points in a cascade of signaling events which drives excessive extracellular matrix protein production, causing fibrosis. Herein the recent breakthroughs which have implicated TLR signaling and the NLRP3 inflammasome in SSc and the novel therapeutic possibilities this introduces to the field will be discussed.

AB - Systemic sclerosis (SSc) is an idiopathic autoimmune disease characterised by inflammation, vascular problems, cytokine dysregulation and ultimately fibrosis, which accounts for poor prognosis and eventual mortality. At present no curative treatments exist, hence there is an urgent need to better understand the aetiology and develop improved therapies accordingly. Although still widely debated, significant evidence points to upregulation of the innate immune response via the activity of Toll-like receptors (TLRs) and the NLRP3 inflammasome as the start points in a cascade of signaling events which drives excessive extracellular matrix protein production, causing fibrosis. Herein the recent breakthroughs which have implicated TLR signaling and the NLRP3 inflammasome in SSc and the novel therapeutic possibilities this introduces to the field will be discussed.

KW - Autoimmunity

KW - Fibrosis

KW - NLRP3 inflammasome

KW - Systemic sclerosis

KW - Toll-like receptors

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