Protein Kinase Serine/Threonine Kinase 24 Positively Regulates Interleukin 17-Induced Inflammation by Promoting IKK Complex Activation

Frontiers in Immunology
Yu JiangXiaojian Wang

Abstract

Interleukin 17 (IL-17) is a key inflammatory cytokine that plays a critical role in tissue inflammation and autoimmune diseases. However, its signaling remains poorly understood. In this study, we identified serine/threonine kinase 24 (Stk24) as a positive modulator of IL-17-mediated signaling and inflammation. Stk24 deficiency or knockdown markedly inhibited IL-17-induced phosphorylation of NF-κB and impaired IL-17-induced chemokines and cytokines expression. Stk24 overexpression greatly enhanced IL-17-induced NF-κB activation and expression of chemokines and cytokines in a kinase activity-independent manner. The IL-17-induced inflammatory response was significantly reduced in Stk24-deficient mice. In addition, the severity of experimental autoimmune encephalomyelitis was markedly reduced in mice with a deficiency of Stk24 in non-hematopoietic cells. We further demonstrated that Stk24 directly interacts with TAK1 and IKKβ and promotes the formation of TAK1/IKK complexes, leading to enhanced IKKβ/NF-κB activation and downstream cytokines and chemokines induction. Collectively, our findings suggest that Stk24 plays an important role in controlling IL-17-triggered inflammation and autoimmune diseases and provides new insight into...Continue Reading

References

Jun 1, 2002·Science·Guoqing Chen, David V Goeddel
Mar 26, 2003·Cell Death and Differentiation·H WajantP Scheurich
Apr 23, 2005·Infection and Immunity·Jing WangTerry W Wright
Aug 14, 2009·Nature·Zong-Ping XiaZhijian J Chen
Oct 15, 2009·Science Signaling·Caini LiuXiaoxia Li
Aug 24, 2010·PloS One·Christopher J RecordWen Hwa Lee
Oct 21, 2010·Nature Immunology·Charles DinarelloChiristopher Gabel
Dec 7, 2010·Cellular Signalling·Seon Hee Chang, Chen Dong
Feb 26, 2011·Immunity·Yoichiro IwakuraSusumu Nakae
Aug 20, 2011·Nature Immunology·Michael J May
Jan 11, 2012·The Biochemical Journal·Stephen J FullerPeter H Sugden
Feb 6, 2013·Journal of Visualized Experiments : JoVE·Sebastian SchildgeChristian Schachtrup
Mar 19, 2013·Annual Review of Biophysics·Johanna Napetschnig, Hao Wu
Apr 6, 2013·Cytokine·Xinyang Song, Youcun Qian
Jun 19, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tomasz HerjanXiaoxia Li
Jul 10, 2013·Nature Medicine·Dominique L P Baeten, Vijay K Kuchroo
Sep 10, 2013·Cytokine·Chunfang GuXiaoxia Li
Jul 2, 2014·The Journal of Experimental Medicine·Yichuan XiaoShao-Cong Sun
Aug 19, 2014·Trends in Pharmacological Sciences·Jianfei YangTetsuya Yamagata
Aug 26, 2014·Nature Reviews. Immunology·Sarah L GaffenDaniel J Cua
Dec 23, 2014·Nature Cell Biology·Chris D MadsenErik Sahai
Sep 16, 2015·The Journal of Cell Biology·Barry J Thompson, Erik Sahai
Jul 18, 2017·F1000Research·Shibali Das, Shabaana Khader

❮ Previous
Next ❯

Methods Mentioned

BETA
ubiquitination
Transfection
PCR
ELISA
Co-immunoprecipitation
Pull-Down
flow cytometry
bronchoalveolar
lavage
genotyping

Software Mentioned

INTERFERin

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.