In the gastrointestinal tract, a dynamic crosstalk between immune cells, intestinal epithelial cells (IECs), and the microbiota is essential to ensure proper organ homeostasis. This crosstalk is largely mediated by cytokines and its dysregulation can lead to pathologies like inflammatory bowel disease (IBD) and intestinal cancer.
Human genome-wide association studies have identified interleukin-26 (IL-26) as a risk locus for IBD. Moreover, IL-26 is over-expressed in IBD lesions. However, The in vivo functions of this cytokine remain largely uncharacterized largely due to its absence in rodents. Interestingly, the zebrafish possesses a unique homolog of the human IL-26 gene. Therefore, in this project, we exploit the zebrafish to determine whether and how IL-26 plays a role in gut homeostasis.
Employing a multifaceted approach including genetic tools, transcriptomics, gnotobiotic methods, microscopy, and bacterial infections, we found that il26-/- larvae display increased IEC proliferation and DNA damage in a microbiota-dependant manner. In order to unravel the underlying mechanisms, we are profiling the composition of the microbiota.
These findings contribute to a comprehensive understanding of IL-26’s impact on gut homeostasis. This sheds a light on potential therapeutic avenues for diseases involving dysregulated immune responses in the gastrointestinal tract.
