TNF and rheumatoid arthritis: To clarify the potential mechanism by which EIE-2 regulates Tregs, we investigated signaling pathways related to RA and Tregs using models corresponding to the active phase of RA (CIA rats, carrageenan-induced paw swelling mice, and TNF-α-induced in isolated primary spleen lymphocyte Tregs reduction model), as well as models corresponding to the inactive phase of RA (control mice and in isolated primary spleen lymphocyte Treg increase model).