Toll-like receptors (TLRs) are evolutionarily conserved receptors essential for the
host defence against pathogens. Both immune and non-immune cells can express TLRs,
although at different levels. Systemic sclerosis (SSc) is a chronic disease in which
autoimmunity, dysregulated profibrotic mediator release and activation of fibroblasts
lead to dysregulated collagen deposition and fibrosis. There is now increasing knowledge
that the innate immune system and, in particular, TLRs take a part in SSc pathogenesis.
The list of endogenous ligands that can stimulate TLRs in SSc is growing: these ligands
represent specific danger-associated molecular patterns (DAMPs), involved either in
the initiation or the perpetuation of inflammation, and in the release of factors
that sustain the fibrotic process or directly stimulate the cells that produce collagen
and the endothelial cells. This review reports evidences concerning TLR signalling
involvement in SSc. We report the new DAMPs, as well as the TLR-linked pathways involved
in disease, with emphasis on type I interferon signature in SSc, the role of plasmacytoid
dendritic cells (pDCs) and platelets. The dissection of the contribution of all these
pathways to disease, and their correlation with the disease status, as well as their
values as prognostic tools, can help to plan timely intervention and design new drugs
for more appropriate therapeutic strategies.
