TNF and arthritic joint disease: While TNF-TNFRI interaction-mediated signaling events are generally proinflammatory, treatment with the TNFRII-selective fusion protein EHD2-sc-mTNFR2, which specifically binds to and activates TNFRII but has no effect on TNFRI, induces expansion of both CD4+ and CD8+ regulatory T cells (Tregs) in vivo, results in anti-inflammatory responses, and reduces the severity of arthritis in a mouse model of CIA [44].