SOCS3 and Splenomegaly: SOCS3 has been shown to dock directly to the GP130 subunit of the IL-6R to suppress signaling (182), with mice harboring a specific mutation at this site (Y759F) displaying similar splenomegaly, lymphadenopathy, B and T cell defects and autoimmune arthritis to SOCS3-deficient animals (183), highlighting the key role of perturbed IL-6R signaling.