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Brugman, S.

Publications and source records attributed to Brugman, S..

3 recordsLinked to original sources

IL-26 from ILCs regulates early-life gut epithelial homeostasis by shaping microbiota composition

Animals host symbiotic microbial communities that shape gut health. However, how the host immune system and microbiota interact to regulate epithelial homeostasis, particularly during early development, remains unclear. Human interleukin-26 (IL-26) is associated with gut inflammation and has intrinsic bactericidal activity in vitro, yet its in vivo functions are largely unknown, primarily due to its absence in rodents. To examine the role of IL-26 in early life, we used zebrafish and found that gut epithelial cells in il26-/- larvae exhibited increased proliferation and DNA damage, faster turnover, and an altered abundance of cell populations. This epithelial dysregulation occurred independently of the IL-26 canonical receptor and resulted from dysbiosis in il26-/-. Moreover, IL-26 bactericidal activity was conserved in zebrafish. Our findings suggest that IL-26 directly regulates microbiota composition through this property. We further identified innate lymphoid cells (ILCs) as the primary source of IL-26 at this developmental stage. These findings establish IL-26 as a central player in a regulatory circuit linking the microbiota, ILCs, and intestinal epithelial cells to maintain gut homeostasis during early life.

immunology↗

Interleukin-22 in enteroendocrine cells controls early-life gut motility through interactions with the microbiota

The gut microbiota, immune system, and enteric nervous system tightly interact to regulate adult gut physiology. Yet the mechanisms establishing gut physiology during development remain unknown. Here, we report that in developing zebrafish, enteroendocrine cells produce IL-22 in response to microbial signals before lymphocytes populate the gut. In larvae, IL-22 is crucial to set gut microbiota composition, and ghrelin hormone expression to promote gut motility. IL-22 developmental function depends on its ability to modulate gut microbiota, as bacterial transfer from wild-type zebrafish restored gut motility in il22-/- by reestablishing ghrelin hormone expression. Additionally, IL-22-deficient mice show impaired gut motility and reduced ghrelin expression in early life, indicating a conserved function. Altogether, we identify a circuit where enteroendocrine cells regulate gut function via cytokine control of the microbiota, showing how gut physiology is set prior to immune system maturation.

immunology↗

Designing Biological Micro-Sensors with Chiral Nematic Liquid Crystal Droplets

Biosensing using liquid crystals has a tremendous potential by coupling the high degree of sensitivity of their alignment to their surroundings with clear optical feedback. Many existing set-ups use birefringence of nematic liquid crystals, which severely limits straightforward and frugal implementation into a sensing platform due to the sophisticated optical set-ups required. In this work, we instead utilize chiral nematic liquid crystal micro-droplets, which show strongly reflected structural colour, as sensing platforms for surface active agents. We systematically quantify the optical response of closely related biological amphiphiles and find unique optical signatures for each species. We detect signatures across a wide range of concentrations (from M to mM), with fast response times (from seconds to minutes). The striking optical response is a function of the adsorption of surfactants in a non-homogeneous manner and the topology of the liquid crystal orientation at the interface requiring a scattering, multidomain structure, which we observe to be different between molecules. We show lab-on-a-chip capability of our method by drying droplets in high-density two-dimensional arrays and simply hydrating the chip to detect dissolved analytes. Finally, we show proof-of-principle in vivo biosensing in the intestinal tracts of live zebrafish larvae, demonstrating CLC droplets show a clear and differential optical response between healthy and inflamed tissues. Our unique approach has great potential in developing on-site detection platforms and detecting biological amphiphiles in living organisms.

bioengineering↗