While tocilizumab is FDA-approved for treatment of SSc-associated ILD through targeting IL-6 signaling, our results implicate E2 and IL-6 as contributors to dermal fibrosis in dcSSc and suggest that effective therapies for dcSSc and other autoimmune diseases likely require concomitant inhibition of both E2 and IL-6. The gene discussed is IL6; the disease is autoimmune disease.