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Author Spotlight: Mapping Cellular Connectivity in the Zebrafish Nervous System During Development and Regeneration
Published on: July 5, 2024
Cd248a and Cd248b in zebrafish participate in innate immune responses
Xianpeng Li1, Ruitong Guo1, Shuaiqi Yang1
1College of Marine Life Sciences, and Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao, China.
Insights
Researchers identified two zebrafish CD248 genes, cd248a and cd248b, which are involved in the fish immune response. These genes regulate pro-inflammatory and anti-inflammatory cytokines, offering insights into CD248 protein function in innate immunity.
Area of Science:
- Molecular Biology
- Immunology
- Zebrafish Genetics
Background:
- CD248 (endosialin) is a transmembrane glycoprotein implicated in various human and mouse cancers and fibrotic diseases.
- No fish orthologs of CD248 have been previously identified.
- Understanding CD248's role in non-mammalian vertebrates can provide broader insights into its function.
Purpose of the Study:
- To identify and characterize CD248 orthologs in zebrafish.
- To investigate the expression patterns and immune functions of zebrafish cd248a and cd248b.
- To explore the role of CD248 in innate immunity.
Main Methods:
- Phylogenetic analysis and conserved synteny to identify zebrafish CD248 orthologs.
- Whole-mount in situ hybridization to analyze gene expression during development.
- Lipopolysaccharide (LPS) challenge to study immune response.
- Protein localization studies and overexpression/deficiency experiments to assess functional roles in cytokine regulation.
Main Results:
- Zebrafish possess two CD248 orthologs, cd248a and cd248b, identified through phylogenetic and synteny analyses.
- Both genes show dynamic expression during zebrafish development and are upregulated upon LPS challenge.
- Overexpression of cd248a/cd248b induces pro-inflammatory cytokines, while their deficiency downregulates pro-inflammatory and upregulates anti-inflammatory cytokines, particularly after LPS treatment.
Conclusions:
- Zebrafish cd248a and cd248b are functional orthologs of human CD248.
- These genes play a significant role in regulating the innate immune response in zebrafish.
- The findings contribute to understanding the evolutionary conservation and function of CD248 in immunity.
Abstract:
CD248, also known as endosialin or tumor endothelial marker 1, is a type I single transmembrane glycoprotein. CD248 has been demonstrated to be upregulated in cancers, tumors and many fibrotic diseases in human and mice, such as liver damage, pulmonary fibrosis, renal fibrosis, arthritis and tumor neovascularization. However, no definite CD248 orthologs in fish have been documented so far. In this study, we report the identification of cd248a and cd248b in the zebrafish. Both the phylogenetic analysis and the conserved synteny strongly suggested that zebrafish cd248a and cd248b are orthologs of the human CD248. Both cd248a and cd248b exhibited similar and dynamic expression pattern in early development, both genes had weak maternal expression, the zygotic transcripts were first seen in anterior somites and head mesenchyme, then shifted to eyes and head mesenchyme, later expanded to branchial arches, and gradually declined with development. The expression profiles of cd248a and cd248b were upregulated upon LPS (Lipopolysaccharide) challenge. Both Cd248a protein and Cd248b protein were localized on the cell membrane and cytoplasm, and overexpression of cd248a and cd248b induced the expression of pro-inflammatory cytokines, in vitro and in vivo. Moreover, deficiency of cd248a or cd248b both downregulated the expression of pro-inflammatory cytokines and upregulated anti-inflammatory cytokine. Additionally, loss of cd248a or cd248b both downregulated the expression of pro-inflammatory cytokines after LPS treatment. Taken together, these results indicated that cd248a and cd248b in zebrafish were involved in immune response and would provide further information to understand functions of Cd248 protein in innate immunity of fish.
