We report that robust changes in cytokine signal transduction occur during the progression of SLE in multiple immune cell subtypes including increased T cell responsiveness to IL-10 and ablation of Stat1 responses to IFNα, IFNγ, IL-6, and IL-21, Stat3 responses to IL-6, Stat5 responses to IL-15, and Stat6 responses to IL-4. Here, IL10 is linked to systemic lupus erythematosus.