0000000000505879
AUTHOR
Franck J. Barrat
RNA recognition by human TLR8 can lead to autoimmune inflammation
High expression level of human TLR8 in mice results in spontaneous, multiorgan inflammation attributable in part to increased DC activation.
Autoimmune skin inflammation is dependent on plasmacytoid dendritic cell activation by nucleic acids via TLR7 and TLR9
Lupus-prone mice develop a chronic inflammatory response to cutaneous injury that depends on the production of type I interferon, TLR7, and TLR9.
Plasmacytoid dendritic cells promote systemic sclerosis with a key role for TLR8
Systemic sclerosis (SSc) is a multisystem life-threatening fibrosing disorder that lacks effective treatment. The link between the inflammation observed in organs such as the skin and profibrotic mechanisms is not well understood. The plasmacytoid dendritic cell (pDC) is a key cell type mediating Toll-like receptor (TLR)-induced inflammation in autoimmune disease patients, including lupus and skin diseases with interface dermatitis. However, the role of pDCs in fibrosis is less clear. We show that pDCs infiltrate the skin of SSc patients and are chronically activated, leading to secretion of interferon-α (IFN-α) and CXCL4, which are both hallmarks of the disease. We demonstrate that the s…