TNF and systemic sclerosis: In systemic sclerosis (SSc), IL-22 synergistically works with TNFα to induce the expression of IL-8 and CCL2 in skin fibroblasts, while the simultaneous stimulation of TGF-β1 and IL-17A can lead to an up-regulation of IL-6 expression in fibroblasts from affected skin by nearly a hundredfold (51, 52).