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bioRxiv · 10.1101/334433

Pellino 1 Communicates Intercellular Signaling in Chronic Skin Inflammatory Microenvironment

Lee, C.-W.·Kim, S.·Bae, S.·Park, J.·Ha, G.-H.·Hwang, K.·Kim, H.-S.·Ji, J.-H.·Go, H.
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Abstract

Chronic skin inflammation including psoriasis is a multisystem disease, affecting more than 5% of the general population. Here we show that Pellino 1 (Peli1), a signal-responsive ubiquitin E3 ligase, is highly up-regulated in human psoriatic skin lesions and that increased Peli1 expression correlates with the immunopathogenesis of psoriasis-like chronic skin inflammatory disease. Interestingly, Peli1 directly interacts with interferon regulatory factor 4 (IRF4, a transcription factor that plays pivotal roles in proliferation and cytokine production) and induces lysine 63-mediated ubiquitination. Peli1-mediated IRF4 ubiquitination appears to be a common systemic signaling mechanism shared by lesional keratinocytes, dendritic cells, macrophages, and T cells, generating a feedback relationship between keratinocyte and Th17 cell responses. Conversely, inhibition of Peli1 interferes with IRF4 induction and attenuates immunopathogenic signaling in the psoriasis. In summary, Peli1-mediated ubiquitination is a common immunopathogenic intercellular signaling in psoriasis-like chronic skin inflammatory microenvironment. Thus, targeting Peli1 could be used as a potential strategy for psoriasis treatment.

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Lee, C.-W., Kim, S., Bae, S., Park, J., Ha, G.-H., Hwang, K., Kim, H.-S., Ji, J.-H., Go, H.. 2018-05-30. Pellino 1 Communicates Intercellular Signaling in Chronic Skin Inflammatory Microenvironment. https://doi.org/10.1101/334433

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