| Literature DB >> 33864770 |
Shuai Shao1, Lam C Tsoi2, William R Swindell2, Jiaoling Chen3, Ranjitha Uppala2, Allison C Billi2, Xianying Xing2, Chang Zeng2, Mrinal K Sarkar2, Rachael Wasikowski2, Yanyun Jiang2, Joseph Kirma2, Jingru Sun2, Olesya Plazyo2, Gang Wang3, Paul W Harms4, John J Voorhees2, Nicole L Ward5, Feiyang Ma6, Matteo Pellegrini6, Alexander Merleev7, Bethany E Perez White8, Robert L Modlin9, Bogi Andersen10, Emanual Maverakis7, Stephan Weidinger11, J Michelle Kahlenberg12, Johann E Gudjonsson13.
Abstract
Many inflammatory skin diseases are characterized by altered epidermal differentiation. Whether this altered differentiation promotes inflammatory responses has been unknown. Here, we show that IRAK2, a member of the signaling complex downstream of IL-1 and IL-36, correlates positively with disease severity in both atopic dermatitis and psoriasis. Inhibition of epidermal IRAK2 normalizes differentiation and inflammation in two mouse models of psoriasis- and atopic dermatitis-like inflammation. Specifically, we demonstrate that IRAK2 ties together proinflammatory and differentiation-dependent responses and show that this function of IRAK2 is specific to keratinocytes and acts through the differentiation-associated transcription factor ZNF750. Taken together, our findings suggest that IRAK2 has a critical role in promoting feed-forward amplification of inflammatory responses in skin through modulation of differentiation pathways and inflammatory responses.Entities:
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Year: 2021 PMID： 33864770 PMCID： PMC9423738 DOI： 10.1016/j.jid.2021.03.019
Source DB: PubMed Journal: J Invest Dermatol ISSN： 0022-202X Impact factor: 7.590