Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by abnormal T cell activation and high levels of autoantibody and multi-organ tissue damage including kidney and skin. Its etiology remains unclear. Skin manifestations are frequent in patients with SLE and because of limited understanding of the involved pathogenic mechanisms there is no specific treatment. Skin injury also exists in the lupus-prone MRL/lpr mice. We have recently observed that signaling through tumor necrosis factor (TNF) receptor 1 is involved in the expression of skin injury in the lupus-prone mice and that human or murine lupus serum induces skin inflammation following intradermal injection in normal mice. We propose that components of lupus serum involve TNF receptor 1 to initiate a skin inflammatory process. We propose to determine the nature of SLE serum-induced skin inflammation;identify the component(s) of SLE serum responsible for the skin inflammation;and determine the role of TNFR1 in the development of SLE serum-induced skin inflammation. Our studies will use genetically modified animals and novel TNF receptor signaling inhibitors to shed light on the pathogenesis of skin injury in SLE and suggest novel local therapeutics. Upon the completion of the proposed studies specific inhibitors of TNF receptor signaling will be proposed as novel therapeutics of autoimmune skin lesions.
Skin manifestations are frequent in patients with SLE and because of limited understanding of the involved pathogenic mechanisms there is no specific treatment. Upon the completion of the proposed studies specific inhibitors of TNF receptor signaling will be proposed as novel therapeutics of autoimmune skin lesions.
| Deng, Guo-Min; Beltran, Jessica; Chen, Chen et al. (2013) T cell CD3? deficiency enables multiorgan tissue inflammation. J Immunol 191:3563-7 |
| Deng, Guo-Min; Liu, Lena; Kyttaris, Vasileios C et al. (2010) Lupus serum IgG induces skin inflammation through the TNFR1 signaling pathway. J Immunol 184:7154-61 |
| Deng, Guo-Min; Liu, Lena; Bahjat, Frances Rena et al. (2010) Suppression of skin and kidney disease by inhibition of spleen tyrosine kinase in lupus-prone mice. Arthritis Rheum 62:2086-92 |
| Deng, Guo-Min; Liu, Lena; Tsokos, George C (2010) Targeted tumor necrosis factor receptor I preligand assembly domain improves skin lesions in MRL/lpr mice. Arthritis Rheum 62:2424-31 |
