376 Activation of linear ubiquitination by linear ubiquitin chain assembly complex specifically exacerbates a murine imiquimod-induced psoriasis model

Nuclear factor-κB (NF-κB) is important in inflammatory skin diseases, including contact dermatitis (Th1 inflammation), atopic (Th2 and psoriasis (Th17 inflammation). In fact, molecularly targeted drugs against tumor necrosis factor (TNF), which both upstream downstream of NF-κB have been demonstrated to be effective diseases such as psoriasis. The linear ubiquitination by ubiquitin chain assembly complex (LUBAC), consists HOIL-1L, HOIP SHARPIN, activating IKKβ, essential for TNF/NF-κB signaling. It has that activates TNF/IKKβ/NF-κB signaling, while HOIL-1L inhibits it. this study, investigate the importance signaling we used mice lacking RING1 domain, active site (HOIL-1LΔRING1 mice). these mice, suppressed enhanced. HOIL-1LΔRING1 did not differ from wild-type (WT) control either a Dinitrofluorobenzene-induced model or an MC903-induced model. On other hand, imiquimod-induced model, showed more severe clinical manifestations than controls. To examine whether radio-resistant cells immune cells, generated bone marrow (BM) chimeric mice. When BM WT were transplanted was worse group with when there no difference dermatitis. These results indicate pathogenesis inhibitors targeting may new therapeutic target drug discovery