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The interdependence of selective cues during development of regulatory T cells (Treg cells) in the thymus and their suppressive function remains incompletely understood. Here, we analyzed this interdependence by taking advantage of highly dynamic changes in expression of microRNA 181 family members miR-181a-1 and miR-181b-1 (miR-181a/b-1) during late T-cell development with very high levels of expression during thymocyte selection, followed by massive down-regulation in the periphery. Loss of miR-181a/b-1 resulted in inefficient de novo generation of Treg cells in the thymus but simultaneously permitted homeostatic expansion in the periphery in the absence of competition. Modulation of T-cell receptor (TCR) signal strength in vivo indicated that miR-181a/b-1 controlled Treg-cell formation via establishing adequate signaling thresholds. Unexpectedly, miR-181a/b-1–deficient Treg cells displayed elevated suppressive capacity in vivo, in line with elevated levels of cytotoxic T-lymphocyte–associated 4 (CTLA-4) protein, but not mRNA, in thymic and peripheral Treg cells. Therefore, we propose that intrathymic miR-181a/b-1 controls development of Treg cells and imposes a developmental legacy on their peripheral function.
Background: Biosurfactants are surface-active molecules produced by different microorganisms and display a promising alternative to synthetically derived food emulsifiers. One of these biosurfactants, synthesized by Bacillus subtilis, is the lipopeptide surfactin, which composes a linear fatty acid and cyclic peptide moiety. This study explores the interfacial and emulsion forming properties of surfactin to further characterize its suitability as an O/W emulsifier in food formulations.
Results: Surfactin revealed a high interfacial activity with a reduction of interfacial tension of 83.26 % to 4.21 ± 0.11 mN/m. O/W emulsions (coil = 10 % w/w) were prepared by high-pressure homogenization, which yielded volume-based mean particle sizes below 1 μm already at low emulsifier concentrations of 0.01 % (w/w). Environmental stress experiments revealed that emulsions were stable between pH 6 to pH 9. Furthermore, neither phase separation nor extensive emulsion instability was observed with NaCl addition up to 0.5 M. However, CaCl2 addition (> 3 mM) destabilized surfactin mediated emulsions. Finally, the main emulsion forming and stabilization effect of surfactin was related to its high interfacial activity and the high degree of electrostatic repulsion between the oil droplets (i.e. zeta-potential of up to −100 mV).
Conclusion; In comparison to other natural and synthetic emulsifiers, the results showed that surfactin is a strong candidate to form and stabilize O/W emulsions under the reported conditions.