- Main
IRAK2 Has a Critical Role in Promoting Feed-Forward Amplification of Epidermal Inflammatory Responses
- Shao, Shuai;
- Tsoi, Lam C;
- Swindell, William R;
- Chen, Jiaoling;
- Uppala, Ranjitha;
- Billi, Allison C;
- Xing, Xianying;
- Zeng, Chang;
- Sarkar, Mrinal K;
- Wasikowski, Rachael;
- Jiang, Yanyun;
- Kirma, Joseph;
- Sun, Jingru;
- Plazyo, Olesya;
- Wang, Gang;
- Harms, Paul W;
- Voorhees, John J;
- Ward, Nicole L;
- Ma, Feiyang;
- Pellegrini, Matteo;
- Merleev, Alexander;
- Perez White, Bethany E;
- Modlin, Robert L;
- Andersen, Bogi;
- Maverakis, Emanual;
- Weidinger, Stephan;
- Kahlenberg, J Michelle;
- Gudjonsson, Johann E
Published Web Location
https://doi.org/10.1016/j.jid.2021.03.019Abstract
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.
Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
Main Content
Enter the password to open this PDF file:
-
-
-
-
-
-
-
-
-
-
-
-
-
-