Highlights d A single-cell atlas of BM ILCs and lung ILCs of healthy, infected, and parabiotic mice d Identification of tissue-associated ILC progenitors in neonatal and adult lung d Cells recruited from BM generate the entire spectrum of ILC2s in infected lungs d Local cues imprint the phenotypes of ILC2s differentiating in the adult lung
Psoriasis pathology is driven by the type 3 cytokines IL-17 and Il-22, but little is understood about the dynamics that initiate alterations in tissue homeostasis. Here, we use mouse models, single-cell RNA-seq (scRNA-seq), computational inference and cell lineage mapping to show that psoriasis induction reconfigures the functionality of skin-resident ILCs to initiate disease. Tissue-resident ILCs amplified an initial IL-23 trigger and were sufficient, without circulatory ILCs, to drive pathology, indicating that ILC tissue remodeling initiates psoriasis. Skin ILCs expressed type 2 cytokines IL-5 and IL-13 in steady state, but were epigenetically poised to become ILC3-like cells. ScRNA-seq profiles of ILCs from psoriatic and naïve skin of wild type (WT) and Rag1 -/mice form a dense continuum, consistent with this model of fluid ILC states. We inferred biological "topics" underlying these states and their relative importance in each cell with a generative model of latent Dirichlet allocation, showing that ILCs from untreated skin span a spectrum of states, including a naïve/quiescent-like state and one expressing the Cd74 and Il13 but little Il5. Upon disease induction, this spectrum shifts, giving rise to a greater proportion of classical Il5-and Il13expressing "ILC2s" and a new, mixed ILC2/ILC3-like subset, expressing Il13, Il17, and Il22. Using these key topics, we related the cells through transitions, revealing a quiescence-ILC2-ILC3s state trajectory. We demonstrated this plasticity in vivo, combining an IL-5 fate mouse with IL-17A and IL-22 reporters, validating the transition of IL-5-producing ILC2s to IL-22-and IL-17A-producing cells during disease initiation. Thus, steady-state skin ILCs are actively repressed and cued for a plastic, type 2 response, which, upon induction, morphs into a type 3 response that drives psoriasis. This suggests a general model where specific immune activities are primed in healthy tissue, dynamically adapt to provocations, and left unchecked, drive pathological remodeling.
Background: Clinicians frequently face difficulties when trying to fix bone abnormalities. Gelatin-Alginate (GA) is frequently employed as a carrier because it is non-toxic, biodegradable, and has a three-dimensional network structure. Meanwhile, cerium oxide nanoparticles (nCeO 2 ) demonstrated high antioxidant enzyme simulation activity. Therefore, in order to develop a porous hydrogel scaffold for the application of bone tissue engineering, an appropriate-type GA-nCeO 2 hydrogel scaffold was developed and evaluated. Methods: GA-nCeO 2 hydrogel scaffold was prepared by the lyophilized method and characterized. The surface morphology and cell adhesion of the scaffold were observed by the scanning electron microscope. CCK8 and live-dead staining methods were used to evaluate its biological safety and cell proliferation. Then the osteogenic differentiation in early and late stages was discussed. The expression of osteogenic genes was also detected by RT-PCR. Finally, a bone defect model was made in SD rats, and bone formation in vivo was detected. Results:The results showed that GA-nCeO 2 hydrogel scaffold exhibited a typical three-dimensional porous structure with a mean pore ratio of 70.61 ± 1.94%. The GA-nCeO 2 hydrogel was successfully endowed with simulated enzyme activity including superoxide dismutase (SOD) and catalase (CAT) after the addition of nCeO 2 . Osteoblasts demonstrated superior cell proliferation and adhesion on composite scaffolds, and both mineralization test and gene expression demonstrated the strong osteogenic potential of GA-nCeO 2 hydrogel. The outcomes of hematoxylin and eosin (H&E) staining and Masson trichrome staining in the femoral defect model of SD rats further supported the scaffold's favorable biocompatibility and bone-promoting capacity. Conclusion: Due to its favorable safety, degradability, and bone formation property, GA-nCeO 2 hydrogel was anticipated to be used as a potential bone defect healing material.
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