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
U2 - 10.1016/j.pharmthera.2018.08.003
DO - 10.1016/j.pharmthera.2018.08.003
M3 - Review article
C2 - 30081049
AN - SCOPUS:85051024539
VL - 192
SP - 163
EP - 169
JO - Pharmacology and Therapeutics, Part A: Chemotherapy, Toxicology and
JF - Pharmacology and Therapeutics, Part A: Chemotherapy, Toxicology and
SN - 0163-7258
ER -