TY - JOUR
T1 - IRAK2 Has a Critical Role in Promoting Feed-Forward Amplification of Epidermal Inflammatory Responses
AU - Shao, Shuai
AU - Tsoi, Lam C.
AU - Swindell, William R.
AU - Chen, Jiaoling
AU - Uppala, Ranjitha
AU - Billi, Allison C.
AU - Xing, Xianying
AU - Zeng, Chang
AU - Sarkar, Mrinal K.
AU - Wasikowski, Rachael
AU - Jiang, Yanyun
AU - Kirma, Joseph
AU - Sun, Jingru
AU - Plazyo, Olesya
AU - Wang, Gang
AU - Harms, Paul W.
AU - Voorhees, John J.
AU - Ward, Nicole L.
AU - Ma, Feiyang
AU - Pellegrini, Matteo
AU - Merleev, Alexander
AU - Perez White, Bethany E.
AU - Modlin, Robert L.
AU - Andersen, Bogi
AU - Maverakis, Emanual
AU - Weidinger, Stephan
AU - Kahlenberg, J. Michelle
AU - Gudjonsson, Johann E.
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
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U2 - 10.1016/j.jid.2021.03.019
DO - 10.1016/j.jid.2021.03.019
M3 - Article
C2 - 33864770
AN - SCOPUS:85105447387
SN - 0022-202X
VL - 141
SP - 2436
EP - 2448
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 10
ER -