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Transcriptomic analysis reveals the immune response of human microglia to a soy protein and collagen hybrid
Li Yao1, Jacques Blasi1, Teresa Shippy2
1Department of Biological Sciences, Wichita State University, 1845 Fairmount Street, Wichita, KS 67260, United States.
Abstract:
Inflammatory reactions resulting from spinal cord injury cause significant secondary damage. Microglial cells activate CD4+ T cells via major histocompatibility complex class II (MHCII) molecules. The activated T cells lead to neural tissue damage and demyelination at early stages of spinal cord injury. Control of the inflammatory response may attenuate the injury process. In this study, we compared gene expression in human microglia grown on soy protein-collagen hybrid scaffolds versus collagen scaffolds. Differentially expressed genes (DEGs) were subjected to gene ontology (GO) and pathway enrichment assays. Among down-regulated genes, the "antigen processing and presentation" pathway shows enrichment, primarily due to the down-regulation of MHCII molecules. The DEGs in this pathway show enrichment of binding sites for several transcription factors, with CIITA and IRF8 being the top candidates. The down-regulation of MHCII along with the significant enrichment of the GO term "focal adhesion" among the up-regulated genes helps explain the higher motility of microglial cells on the hybrid scaffold compared with that on the collagen scaffold. Up-regulated genes associated with "focal adhesion" include DNM2, AHNAK, and HYOU1, which have been previously implicated in increased cell motility. Overall, our study indicates that the use of hybrid scaffolds containing soy protein and collagen may modulate the immune response of wounded neural tissue.
Insights
Soy protein-collagen scaffolds modulate microglial immune responses in spinal cord injury. These hybrid scaffolds down-regulate major histocompatibility complex class II (MHCII) molecules, potentially reducing neural tissue damage.
Area of Science:
- Biomaterials Science
- Neuroimmunology
- Regenerative Medicine
Background:
- Spinal cord injury triggers inflammatory responses mediated by microglial cells activating CD4+ T cells via MHCII molecules.
- This microglial activation contributes to secondary neural tissue damage and demyelination.
- Controlling neuroinflammation is crucial for attenuating spinal cord injury progression.
Purpose of the Study:
- To compare gene expression in human microglia cultured on soy protein-collagen hybrid scaffolds versus collagen-only scaffolds.
- To identify differentially expressed genes (DEGs) and associated biological pathways.
- To elucidate the potential of hybrid scaffolds in modulating microglial immune responses.
Main Methods:
- Human microglia cultured on two scaffold types: soy protein-collagen hybrid and collagen.
- Differential gene expression analysis of cultured microglia.
- Gene ontology (GO) and pathway enrichment analyses of DEGs.
Main Results:
- Soy protein-collagen scaffolds down-regulated the "antigen processing and presentation" pathway, primarily via reduced MHCII expression.
- Transcription factors CIITA and IRF8 were identified as key regulators in this pathway.
- Up-regulated genes in the "focal adhesion" pathway (e.g., DNM2, AHNAK, HYOU1) were associated with increased microglial cell motility on hybrid scaffolds.
Conclusions:
- Soy protein-collagen hybrid scaffolds can modulate the immune response in neural tissue following injury.
- Down-regulation of MHCII and enhanced microglial motility suggest a potential therapeutic benefit.
- These findings support the use of hybrid scaffolds for managing neuroinflammation in spinal cord injury.
