國家衛生研究院 NHRI:Item 3990099045/15401

NHRI > National Institute of Environmental Health Sciences > Shau-Ku Huang > Periodical Articles > Item 3990099045/15401

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/15401

Title:	The nuclear cytokine IL-37a controls lethal cytokine storms primarily via IL-1R8-independent transcriptional upregulation of PPARgamma
Other Titles:	The nuclear cytokine IL-37a controls lethal cytokine storms primarily via IL-1R8-independent transcriptional upregulation of PPARγ
Authors:	Wei, R;Han, X;Li, M;Ji, Y;Zhang, L;Christodoulou, MI;Hameed Aga, NJ;Zhang, C;Gao, R;Liu, J;Fu, J;Lu, G;Xiao, X;Liu, X;Yang, PC;McInnes, IB;Sun, Y;Gao, P;Qin, C;Huang, SK;Zhou, Y;Xu, D
Contributors:	National Institute of Environmental Health Sciences
Abstract:	Cytokine storms are crucial in the development of various inflammatory diseases, including sepsis and autoimmune disorders. The immunosuppressive cytokine INTERLEUKIN (IL)-37 consists of five isoforms (IL-37a-e). We identified IL-37a as a nuclear cytokine for the first time. Compared to IL-37b, IL-37a demonstrated greater efficacy in protecting against Toll-like receptor-induced cytokine hypersecretion and lethal endotoxic shock. The full-length (FL) form of IL-37a and the N-terminal fragment, which is processed by elastase, could translocate into cell nuclei through a distinctive nuclear localization sequence (NLS)/importin nuclear transport pathway. These forms exerted their regulatory effects independent of the IL-1R8 receptor by transcriptionally upregulating the nuclear receptor peroxisome proliferator-activated receptor (PPARγ). This process involved the recruitment of the H3K4 methyltransferase complex WDR5/MLL4/C/EBPβ and H3K4me1/2 to the enhancer/promoter of Pparg. The receptor-independent regulatory pathway of the nuclear IL-37a-PPARγ axis and receptor-dependent signaling by secreted IL-37a maintain homeostasis and are potential therapeutic targets for various inflammatory diseases, including sepsis.
Date:	2023-12
Relation:	Cellular and Molecular Immunology. 2023 Dec;20(12):1428-1444.
Link to:	http://dx.doi.org/10.1038/s41423-023-01091-0
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1672-7681&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:001090768300001
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85174891476
Appears in Collections:	[Shau-Ku Huang] Periodical Articles

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