We highlight studies detailing the expression of TNF-α in IL-10 producing B cells that initially appears antithetical to their function, but after further investigation of TNF-α binding dynamics to its two receptors (TNFR1 and TNFR2) that allow for its pleiotropic, opposing signaling pathways, the potential inhibition of the inflammatory pathway while maintaining the homeostatic signaling of the other becomes an apparent solution to many of the autoimmune diseases mediated by TNF-α dysregulation. Here, IL10 is linked to autoimmune disease.