TLR signaling, particularly TLR4, results in inflammatory cell infiltration, B cell activation, polarization toward a Th2/Th17 response, activation of nuclear factor kappa beta (NF-κB), elevated expression of profibrotic cytokines (e.g., IL-4 and IL-6), activation of TGF-β downstream canonical SMAD signaling, and pathological angiogenesis in SSc [55–60]. The gene discussed is NFKB1; the disease is systemic sclerosis.