IL-17 signaling is regulated through intrinsic stability control of mRNA during inflammation

Ryuta Muromoto; Kenji Oritani; Tadashi Matsuda; Ryuta Muromoto; Kenji Oritani; Tadashi Matsuda

doi:10.3934/Allergy.2022014

AIMS Allergy and Immunology

2022, Volume 6, Issue 3: 188-199. doi: 10.3934/Allergy.2022014

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IL-17 signaling is regulated through intrinsic stability control of mRNA during inflammation

1.
Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Kita-Ku Kita 12 Nishi 6, Sapporo 060-0812, Japan
2.
Department of Hematology, International University of Health and Welfare, 4-3 Kouzunomori, Narita, Chiba 286-8686, Japan

Received: 17 August 2022 Revised: 16 September 2022 Accepted: 22 September 2022 Published: 26 September 2022

Interleukin (IL)-17 is a proinflammatory cytokine mainly produced by immune cells, especially activated T-helper 17 cells, which contribute to chronic inflammatory and autoimmune diseases including psoriasis. Although the molecular mechanisms of transcription in IL-17-mediated signaling pathways are well established, post-transcriptional control remains to be elucidated. Notably, IL-17 regulates post-transcriptional modifications, which induce elevated levels of target inflammatory mRNAs. Regnase-1, an endoribonuclease and deubiquitinase, post-transcriptionally downregulates various IL-17-driven signaling pathways, including mRNA stability. The ACT1-TBK1/IKKϵ pathway and ARID5A were induced and activated by IL-17-stimulation, leading to the inhibition of inflammatory mRNA degradation by Regnase-1. In this review, we focus on IL-17-mediated mRNA stabilization of psoriasis-related IκB-ζ and provide novel therapeutic strategies for the treatment of Th17-mediated inflammation and autoimmunity.
- IL-17,
- Th17,
- IκB-ζ,
- Regnase-1,
- mRNA stabilization,
- inflammation
Citation: Ryuta Muromoto, Kenji Oritani, Tadashi Matsuda. IL-17 signaling is regulated through intrinsic stability control of mRNA during inflammation[J]. AIMS Allergy and Immunology, 2022, 6(3): 188-199. doi: 10.3934/Allergy.2022014

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Abstract

Interleukin (IL)-17 is a proinflammatory cytokine mainly produced by immune cells, especially activated T-helper 17 cells, which contribute to chronic inflammatory and autoimmune diseases including psoriasis. Although the molecular mechanisms of transcription in IL-17-mediated signaling pathways are well established, post-transcriptional control remains to be elucidated. Notably, IL-17 regulates post-transcriptional modifications, which induce elevated levels of target inflammatory mRNAs. Regnase-1, an endoribonuclease and deubiquitinase, post-transcriptionally downregulates various IL-17-driven signaling pathways, including mRNA stability. The ACT1-TBK1/IKKϵ pathway and ARID5A were induced and activated by IL-17-stimulation, leading to the inhibition of inflammatory mRNA degradation by Regnase-1. In this review, we focus on IL-17-mediated mRNA stabilization of psoriasis-related IκB-ζ and provide novel therapeutic strategies for the treatment of Th17-mediated inflammation and autoimmunity.

Acknowledgments

The authors thank Editage (www.editage.com) for English language editing. This study was supported in part by Grant-in-Aid for scientific research 20K07010 (R. M.) and 19H03364 (T.M.) from Ministry of Education, Culture, Sports, Science and Technology of Japan.

Conflict of interest

All authors declare no conflicts of interest in this paper.

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