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Transcriptomic and Bioinformatic Analyses Identifying a Central Mif-Cop9-Nf-kB Signaling Network in Innate Immunity
Laura La Paglia1, Mirella Vazzana2, Manuela Mauro2
1Istituto di Calcolo e Reti ad Alte Prestazioni-Consiglio Nazionale delle Ricerche, Via Ugo La Malfa 153, 90146 Palermo, Italy.
International Journal of Molecular Sciences
|February 25, 2023
Summary
The innate immune response in C. robusta involves macrophage migration inhibitory factors (CrMifs), the COP9 signalosome (CSN), and the NF-kB pathway. This study reveals a conserved link between these components during LPS-induced inflammation.
Area of Science:
- Immunology
- Molecular Biology
- Marine Biology
Background:
- The ascidian C. robusta serves as a model organism for innate immunity research.
- LPS triggers inflammatory reactions and innate immune gene expression in C. robusta hemocytes.
- The NF-kB pathway, crucial for inflammation, is conserved across species, involving the COP9 signalosome (CSN) complex.
Purpose of the Study:
- To investigate the molecular players and temporal dynamics of Mif cytokines, CSN signaling, and the NF-kB pathway in C. robusta.
- To elucidate the role of these pathways in LPS-mediated inflammatory responses.
- To explore the regulatory mechanisms, including microRNAs, involved in this immune response.
Main Methods:
- Bioinformatics and in-silico analyses.
- In-vivo LPS exposure in C. robusta.
- Next-generation sequencing (NGS) and quantitative real-time PCR (qRT-PCR).
- Phylogenetic and STRING analyses.
Main Results:
- A biphasic activation pattern of the inflammatory response was observed via qRT-PCR.
- Phylogenetic and STRING analyses confirmed an evolutionarily conserved functional link between the Mif-CSN-NF-kB axis.
- The study identified conserved signaling components and regulatory roles of non-coding molecules like miRNAs.
Conclusions:
- The Mif-CSN-NF-kB axis is functionally conserved in C. robusta's innate immune response to LPS.
- This pathway is finely regulated by non-coding molecules such as microRNAs.
- C. robusta provides valuable insights into conserved mechanisms of innate immunity.

