2. Academic Validation
  3. IL-18 signaling is regulated by caspase 6/8 and IL-18BP in turbot (Scophthalmus maximus)

IL-18 signaling is regulated by caspase 6/8 and IL-18BP in turbot (Scophthalmus maximus)

  • Int J Biol Macromol. 2024 Oct;278(Pt 4):135015. doi: 10.1016/j.ijbiomac.2024.135015.
Chao Yu 1,  Hang Xu 2,  Shuai Jiang 3,  Li Sun 4
Affiliations

Affiliations

  • 1 CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, CAS Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China; School of Foundational Education, University of Health and Rehabilitation Sciences, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology, Qingdao, China; College of Earth and Planetary Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • 2 CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, CAS Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology, Qingdao, China; College of Earth and Planetary Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • 3 CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, CAS Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology, Qingdao, China; College of Earth and Planetary Sciences, University of Chinese Academy of Sciences, Beijing, China. Electronic address: sjiang@qdio.ac.cn.
  • 4 CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, CAS Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology, Qingdao, China; College of Earth and Planetary Sciences, University of Chinese Academy of Sciences, Beijing, China. Electronic address: lsun@qdio.ac.cn.
PMID: 39181350 DOI: 10.1016/j.ijbiomac.2024.135015
Abstract

Interleukin (IL)-18 is synthesized as a precursor that requires intracellular processing to become functionally active. In human, IL-18 is processed by Caspase 1 (CASP1). In teleost, the maturation and signal transduction mechanisms of IL-18 are unknown. We identified two IL-18 variants, IL-18a and IL-18b, in turbot. IL-18a, but not IL-18b, was processed by CASP6/8 cleavage. Mature IL-18a bound specifically to IL-18 Receptor (IL-18R) α-expressing cells and induced IL-18Rα-IL-18Rβ association. Bacterial infection promoted IL-18a maturation in a manner that required CASP6 activation and correlated with gasdermin E activation. The mature IL-18a induced proinflammatory cytokine expression and enhanced Bacterial clearance. IL-18a-mediated immune response was suppressed by IL-18 binding protein (IL-18BP), which functioned as a decoy receptor for IL-18a. IL-18BP also functioned as a pathogen pattern recognition receptor and directly inhibited pathogen Infection. Our findings revealed unique mechanism of IL-18 maturation and conserved mechanism of IL-18 signaling and regulation in turbot, and provided new insights into the regulation and function of IL-18 related immune signaling.

Keywords

Caspase; Immune defense; Interleukin 18; Interleukin 18 binding protein; Interleukin 18 receptor; Teleost.

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