Table 1.
An overview of tumour necrosis factor (TNF) superfamily members in autoimmune diseases
| Role in disease | ||
|---|---|---|
| Antigen | Expression | Therapeutic outcome |
| CD27–CD70 | CD27hi B↑ in SLE [17,18]; sCD27↑ in SLE [19]; CD4+CD70+↑ in lupus [21] and RA [23] | Anti-CD70 antibodies: EAE↓[22] and RA↓[24] |
| CD30–CD153 | sCD30↑ and sCD153↑ in RA [34–36], MS [38,39], SLE [40], Sjögren's syndrome [41] and diabetes [42] | Anti-CD30L: diabetes↓[42] |
| CD40–CD40L | CD40+ epithelial cells↑ in Graves' disease [54], autoantibodies to CD40L↑ in SLE patients↑[61,62]; CD40+ T cells ↑in NOD mice [58] | Anti-CD40L: experimental thyroiditis↓[55], type I diabetes↓[57], CIA↓[59], lupus↓[60], human SLE↓[61,62], EAE↓[64] |
| CD134–CD134L | CD134+ CD4+ T cells↑ in SLE patients [69], RA patients [71], and myasthenia gravis patients [77]; CD134+ cells↑ in the CNS of EAE mice and MS patients [73] | Anti-CD134L: CIA↓ (70) and diabetes↓[78]; anti-CD134: EAE↑[74,75] |
| CD137–CD137L | sCD137↑ and sCD137L↑ in sera of RA [89,90] and MS [91] patients | Lupus↓[92,93], EAE↓[96], RA↓[97], EAU↓[103] |
| Fas–FasL | Fas+ and FasL+ cells↑ on glial cells, macrophages, lymphocytes in MS brain [135,140]; acinar cells of salivary glands of Sjögren's syndrome [141], CD4+ and CD8+ T cells of SLE [142,143], RA [136,139], Sjögren's syndrome [136] and MS [144] patients | Fas- and FasL-deficient mice: autoimmune diseases↑[125,126]; adenovirus carrying FasL: apoptosis↑[139], RA↓[139]; anti-Fas mAb: RA↓[117,145–147]; deletion of IFN-γ or IFN-γR in MRL/lpr mice:lupus↓[150,152] |
| TNF-α–TNFR1 | sTNFR1↑ in SLE patients [170]; TNFR1+ cells↑ in skin lesions of MRL/lpr mice [172] | TNFR1-Ig: EAN↓[161], CIA↓[162,163], EAE↓[167–169]; TNFR1−/−TNFR2−/− NZB/F1 mice: lupus↑[171] |
| DR5–TRAIL | DR5+ synovial fibroblasts ↑ in arthritic joints [195] | sDR5: arthritis↑[190]; TRAIL gene transfer: arthritis↑[190–192]; TRAIL−/− mice: arthritis ↑[193], diabetes↑[197]; transfer of TRAIL-pulsed DCs: arthritis↓[194]; sTRAIL: EAE↓[196], diabetes↑[197] |
↑: increase; ↓: decrease; sCD30, soluble CD30. SLE: systemic lupus erythematosus; RA: rheumatoid arthritis; MRL: Murphy Roths Large; TNFR: TNF receptor; EAN: experimental autoimmune neuritis; TRAIL: TNF-α-related apoptosis-inducing ligand; CIA: collagen-induced arthritis; IFN: interferon; mAb: monoclonal antibody; EAU: experimental autoimmune uveoretinitis; MS: multiple sclerosis; NOD: non-obese diabetic; CNS: central nervous system; NZB: New Zealand black.