In the normal small intestine, the levels of SFB and Th17 cells are both held constant because they counterbalance each other. Th17 cells release IL-17 to limit unwanted SFB expansion, while decreasing the number of SFBs facilitates the restrictive action of Th17 cells. The research group found that this elaborate control system was due to the presence of healthy IECs. IECs lacking the IκBζ gene do not exert antibacterial effects in response to IL-17, even though the cytokine is abundantly produced by an increase in Th17 cells. They demonstrated that the lack of IκBζ in IECs leads to an impairment of two IL-17-mediated defense mechanisms in the intestine: the production of IgA and the maintenance of Paneth cell integrity.
Intestinal epithelial cells are aligned in a single layer. This thin layer is beneficial for nutrient uptake, but vulnerable to invasion. It requires a strong defense mechanism against invading pathogens. In addition, these cells must control the growth of microbes flexibly as needed.”
Soh Yamazaki, Ph.D., senior author of the article, associate professor, Toho University School of Medicine
“We hope that our study will lead to the development of a new strategy to treat inflammatory diseases by manipulating IκBζ function,” said last author Hiroyasu Nakano, MD, Ph.D. Professor at the School of Medicine of Toho University. The result was published online on August 24, 2022 in the journal Mucosal immunology.
Yamazaki, S. et al. (2022) IκBζ controls the IL-17-triggered gene expression program in intestinal epithelial cells that limits SFB colonization and prevents Th17-associated pathologies. Mucosal immunology. doi.org/10.1038/s41385-022-00554-3.