Introduction 2.1. TNF ligands and receptors in immunity and autoimmunity 3. TWEAK (TNF-like Weak Inducer of Apoptosis), a novel TNF family member 4. Fn14, the cognate receptor for TWEAK 5. Mechanisms of TWEAK signaling 6. TWEAK-Fn14 interactions and the induction of apoptosis 7. Angiogenic and pro-inflammatory effects of TWEAK on primary cells and cell lines 7.1. Angiogenic effects of TWEAK on endothelial cells 7.2. Pro-inflammatory effects of TWEAK on endothelial cells 7.3. Pro-inflammatory effects of TWEAK on astrocytes 7.4. Pro-inflammatory effects of TWEAK on synoviocytes and fibroblasts 8. The role of TWEAK in autoimmune disease 8.1. TWEAK and autoimmune neurological disease 8.2. TWEAK in systemic lupus erythematosus 8.2. 1. The role of TWEAK-inducible chemokines in lupus nephritis 9. Is TWEAK involved in the pathogenesis of tolerance breakdown and target organ damage in SLE? 9.1. TWEAK/Fn14 interactions and tolerance to nuclear antigens 9.2. TWEAK/Fn14 interactions and lupus nephritis 9.3. TWEAK/Fn14 interactions and neuropsychiatric SLE 10. Perspective