Biomolecules from snail mucus (Helix aspersa) conjugated gold nanoparticles, exhibiting potential wound healing and anti-inflammatory activity.

In this work, for the first time, snail slime from garden snails "Helix Aspersa Müller", has been used to induce the formation of eco-friendly gold nanoparticles (AuNPs-SS) suitable for biomedical applications. An AuNPs-SS comprehensive investigation was performed and AuNPs with an average particle size of 14 ± 6 nm were observed, stabilized by a slime snail-based organic layer. Indeed, as recognized in high-resolution MALDI-MS analyses, and corroborated by FESEM, UV-Vis, ATR-FTIR, and XPS results, it was possible to assess the main presence of peptides and amino acids as the main components of the slime, that, combined with the AuNPs confers on them interesting properties. More specifically, we tested, in vitro, the AuNPs-SS safety in human keratinocytes and their potential effect on wound healing as well as their anti-inflammatory properties in murine macrophages. Moreover, the AuNPs-SS treatment resulted in a significant increase of the urokinase-type plasminogen activator receptor (uPAR), essential for keratinocyte adhesion, spreading, and migration, together with the reduction of LPS-induced IL1-ß and IL-6 cytokine levels, and completely abrogated the synthesis of inducible nitric oxide synthase (iNOS).

Combined multidimensional single-cell protein and RNA profiling dissects the cellular and functional heterogeneity of thymic epithelial cells.

The network of thymic stromal cells provides essential niches with unique molecular cues controlling T cell development and selection. Recent single-cell RNA sequencing studies have uncovered previously unappreciated transcriptional heterogeneity among thymic epithelial cells (TEC). However, there are only very few cell markers that allow a comparable phenotypic identification of TEC. Here, using massively parallel flow cytometry and machine learning, we deconvoluted known TEC phenotypes into novel subpopulations. Using CITEseq, these phenotypes were related to corresponding TEC subtypes defined by the cells' RNA profiles. This approach allowed the phenotypic identification of perinatal cTEC and their physical localisation within the cortical stromal scaffold. In addition, we demonstrate the dynamic change in the frequency of perinatal cTEC in response to developing thymocytes and reveal their exceptional efficiency in positive selection. Collectively, our study identifies markers that allow for an unprecedented dissection of the thymus stromal complexity, as well as physical isolation of TEC populations and assignment of specific functions to individual TEC subtypes.

Embryonic keratin19+ progenitors generate multiple functionally distinct progeny to maintain epithelial diversity in the adult thymus medulla.

The thymus medulla is a key site for immunoregulation and tolerance, and its functional specialisation is achieved through the complexity of medullary thymic epithelial cells (mTEC). While the importance of the medulla for thymus function is clear, the production and maintenance of mTEC diversity remains poorly understood. Here, using ontogenetic and inducible fate-mapping approaches, we identify mTEC-restricted progenitors as a cytokeratin19+ (K19+) TEC subset that emerges in the embryonic thymus. Importantly, labelling of a single cohort of K19+ TEC during embryogenesis sustains the production of multiple mTEC subsets into adulthood, including CCL21+ mTEClo, Aire+ mTEChi and thymic tuft cells. We show K19+ progenitors arise prior to the acquisition of multiple mTEC-defining features including RANK and CCL21 and are generated independently of the key mTEC regulator, Relb. In conclusion, we identify and define a multipotent mTEC progenitor that emerges during embryogenesis to support mTEC diversity into adult life.