RESUMEN
No other issue has preoccupied the entire world in the last two years as much as the Corona pandemic. Accordingly, the topic of the immune system and how to keep it strengthened to avoid infection came into focus. And indeed, we can observe that the appearance of the skin suffers greatly when we have caught an infection. But there are also chronic skin conditions that are immunologically caused and where there is no infection. Psoriasis is such a condition. Six out of 2000 people asked in the UK suffer from psoriasis, independent from age or gender (Mintel). Psoriasis is currently not curable. We can only try to alleviate the symptoms. Here we show how a medicinal mushroom used for thousands of years can provide relief. It regulates the immune system and the skin microbiota, and can thus reduce psoriasis. This concept coincides with the consumer's desire for a natural solution to their condition. [ FROM AUTHOR] Copyright of SOFW Journal (English version) is the property of Verlag fuer chemische Industrie H. Ziolkowsky GmbH and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
RESUMEN
Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathology, and it remains unclear whether T cells contribute to disease pathology. Here, we combined single-cell transcriptomics and single-cell proteomics with mechanistic studies to assess pathogenic T cell functions and inducing signals. We identified highly activated CD16(+) T cells with increased cytotoxic functions in severe COVID-19. CD16 expression enabled immune-complex-mediated, T cell receptor-independent degranulation and cytotoxicity not found in other diseases. CD16(+) T cells from COVID-19 patients promoted microvascular endothelial cell injury and release of neutrophil and monocyte chemoattractants. CD16(+) T cell clones persisted beyond acute disease maintaining their cytotoxic phenotype. Increased generation of C3a in severe COVID-19 induced activated CD16(+) cytotoxic T cells. Proportions of activated CD16(+) T cells and plasma levels of complement proteins upstream of C3a were associated with fatal outcome of COVID-19, supporting a pathological role of exacerbated cytotoxicity and complement activation in COVID-19.
RESUMEN
Background: Acute kidney injury (AKI) is frequently observed in critically ill patients and is associated with a poor prognosis. AKI has recently moved into the focus of interest during the SARS-CoV-2 pandemic as high rates of AKI have been reported in severe COVID-19. We aimed to delineate cell type-specific molecular phenotypes associated with human AKI, including COVID-associated AKI. Methods: We analyzed human kidney tissues using histology and single-nuclei RNA sequencing. Samples included kidney biopsies obtained within 2 hours post mortem from patients who succumbed to critical illness with and without evidence of AKI. Samples also included tumor-adjacent normal kidney tissues obtained during surgeries. AKI cases included patients with severe courses of COVID-19 (COVID AKI) and patients with other types of critical illness associated with systemic inflammation (Non-COVID AKI). Postmortem kidney tissues obtained 30 min, 1 hour and 2 hours after death from a brain-dead patient without AKI were analyzed to assess the impact of post-mortem effects. Results: Single-nuclei sequencing from kidney tissues yielded data of high transcriptional depth, which allowed transcriptome-based identification and de-novo spatial reconstruction of kidney cells. Principal component and differential gene expression analyses indicated that the presence of clinically confirmed AKI was the primary driver of global kidney transcriptomes and that different molecular subtypes of AKI existed. In contrast, the sampling time post-mortem and the presence of COVID-19 had minor effects. Subclustering analyses of different kidney cell types identified subclasses of cells representing injured kidney tubular cells, which were marked by distinct biomarker expression and expression signatures signifying intrinsic responses to inflammation, an induction of epithelial-to-mesenchymal transition, and an upregulation of hitheto unrecognized novel receptor-ligand pairs. Conclusions: We provide the first cell type-specific molecular atlas of human AKI, revealing unanticipated disease subtypes and cell type-specific injury patterns.