TNF and systemic sclerosis: In the skin of SSc patients, the infiltration and activation of plasmacytoid dendritic cells (pDCs) via PI3Kδ pathway leads to aberrant expression of TLR8 (otherwise not expressed in pDCs) that induces CXCL4, IFN-α, IL6, and TNF secretion contributing to skin fibrosis and autoimmunity (87).