Immune Response to Injury Drives Regeneration of Sensory Neurons

Immune Response to Injury Drives Regeneration of Sensory Neurons

Table of Contents

What are Commensal Bacteria?

Our immune system is designed to defend us against the microbial world – but what you may not know is that activation of our immune response is also critical for tissue repair during injury. The convergence of these roles is particularly important at barrier tissues, such as the skin, which host a rich community of bacteria that can get introduced into the body upon injury. 

Interestingly, pathogens like S. aureus, a cause of staph infections, can colonize the skin in a harmless manner before ever becoming pathogenic. These “commensal” bacteria recruit a type of T cell, Th17, to the skin, but upon infection, these recruited Th17 cells do not provide any special protection from infection. So what purpose do these microbe-recruited T cells serve?

Microbiome-Induced Th17 Cells are Essential for Neuronal Regeneration in Barrier Tissues 

In response to stress, like an injury, Th17 cells trigger repair-focused immune responses, promoting subsequent tissue regeneration at the damaged site. Barrier tissues are known to be rich in sensory nerve fibers and the regeneration of these fibers is important to facilitate the perception of touch, pain, and itch. However, the exact interplay between Th17 cells recruited by microbiota and nerve regeneration remains unclear.

In a recent research article in Cell, Enamorado et. al. used bulk RNA sequencing (RNAseq) and pathway analysis to identify microbiota-induced gene signatures in Th17 cells that facilitate nerve interaction and regeneration. After alignment of the sequenced data, feature count generation, and normalization, differentially expressed genes (DEGs) were identified using the DESeq2 package and subset with an FDR and fold change cut-offs of 0.05 and 2, respectively. 

RNA-Seq Uncovers Transcriptomic Signatures of Activated Th17 Cells

The microbiome-induced Th17 cells displayed over 3000 DEGs relative to the control group, with many of the upregulated transcripts being directly involved in tissue repair, neuronal interaction, and regeneration. Functional enrichment analysis also identified gene ontology terms related to nerve interaction and regeneration, response to wounding, and morphogenesis of epithelium. 

Overall, this demonstrates that a microbiome-immune interaction, perhaps unexpectedly, promotes nerve regeneration in the skin. This insight may provide novel therapeutic strategies to recover damaged neurons and enhance sensory recovery after injury to improve the standard of care for patients. 

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Haider M. Hassan, Data Scientist, Bridge Informatics

Haider is one of our premier data scientists. He provides bioinformatic services to clients, including high throughput sequencing, data pre-processing, analysis, and custom pipeline development. Drawing on his rich experience with a variety of high-throughput sequencing technologies, Haider analyzes transcriptional (spatial and single-cell), epigenetic, and genetic landscapes.

Before joining Bridge Informatics, Haider was a Postdoctoral Associate at the London Regional Cancer Centre in Ontario, Canada. During his postdoc, he investigated the epigenetics of late-onset liver cancer using murine and human models. Haider holds a Ph.D. in biochemistry from Western University, where he studied the molecular mechanisms behind oncogenesis. Haider still lives in Ontario and enjoys spending his spare time visiting local parks. If you’re interested in reaching out, please email [email protected] or [email protected].

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