TNF and systemic sclerosis: Adiponectin is known to interfere with the TGF-β/SMAD signaling cascade, thereby inhibiting collagen production and fibroblast activation—two hallmarks of SSc pathophysiology.11,49 Moreover, adiponectin modulates immune function by suppressing the secretion of IL-6 and TNF-α and inhibiting macrophage activation,12,51 which are relevant to the chronic inflammatory milieu observed in SSc.