Long-term tolerance to skin commensals is established neonatally through a specialized dendritic cell subgroup.

Early-life establishment of tolerance to commensal bacteria at barrier surfaces carries enduring implications for immune health but remains poorly understood. Here, we showed that tolerance in skin was controlled by microbial interaction with a specialized subset of antigen-presenting cells. More particularly, CD301b+ type 2 conventional dendritic cells (DCs) in neonatal skin were specifically capable of uptake and presentation of commensal antigens for the generation of regulatory T (Treg) cells. CD301b+ DC2 were enriched for phagocytosis and maturation programs, while also expressing tolerogenic markers. In both human and murine skin, these signatures were reinforced by microbial uptake. In contrast to their adult counterparts or other early-life DC subsets, neonatal CD301b+ DC2 highly expressed the retinoic-acid-producing enzyme, RALDH2, the deletion of which limited commensal-specific Treg cell generation. Thus, synergistic interactions between bacteria and a specialized DC subset critically support early-life tolerance at the cutaneous interface.

Progression of Self-Assembly of Amelogenin Protein Supramolecular Structures in Simulated Enamel Fluid.

Mechanisms of protein-guided mineralization in enamel, leading to organized fibrillar apatite nanocrystals, remain elusive. In vitro studies reveal recombinant human amelogenin (rH174), a matrix protein templating this process, self-assembles into a variety of structures. This study endeavors to clarify the self-assembly of rH174 in physiologically relevant conditions. Self-assembly in simulated enamel fluid was monitored up to 2 months. At alkali (7.3-8.7) and acidic (5.5-6.1) pH ranges, a distinct progression in formation was observed from nanospheres (17-23 nm) to intermediate-length nanorods, concluding with the formation of long 17-18 nm wide nanoribbons decorated with nanospheres. Assembly in acidic condition progressed quicker to nanoribbons with fewer persistent nanospheres. X-ray diffraction exhibited reflections characteristic of antiparallel ß-sheets (4.7 and 9.65 Å), supporting the model of amyloid-like nanoribbon formation. This is the first observation of rH174 nanoribbons at alkaline pH as well as concurrent nanosphere formation, indicating both supramolecular structures are stable together under physiological conditions.