Allergic diseases, which include asthma, allergic skin diseases, allergic rhinitis and allergic conjunctivitis, have already garnered worldwide public health attention over recent decades. ...Mesenchymal stem cells (MSCs) have gradually emerged as a potential method for treating allergic diseases due to their immunosuppressive characteristics, tissue repair ability and secretion of various biological factors. This potential of MSC-based therapy has been confirmed in clinical and preclinical studies, which report the therapeutic benefits of MSCs for various allergic diseases and explore the antiallergic mechanisms. In this review, we focus on the discoveries and biological mechanisms of MSCs as a therapeutic tool in allergic diseases. We discuss the challenges of conducting MSC studies as well as future directions.
Summary
Artemisinin, isolated from Artemisia annua, is recommended as the preferred drug to fight malaria. Previous research showed that jasmonate (JA)‐mediated promotion of artemisinin accumulation ...depended on light. However, the mechanism underlying the interaction of light and JA in regulating artemisinin accumulation is still unknown.
We identified a WRKY transcription factor, AaWRKY9, using transcriptome analysis. The glandular trichome‐specific AaWRKY9 positively regulates artemisinin biosynthesis by directly binding to the promoters of AaDBR2 and AaGSW1.
The key regulator in the light pathway AaHY5 activates the expression of AaWRKY9 by binding to its promoter. In addition, AaWRKY9 interacts with AaJAZ9, a repressor in the JA signalling pathway. AaJAZ9 represses the transcriptional activation activity of AaWRKY9 in the absence of methyl jasmonate. Notably, in the presence of methyl jasmonate, the transcriptional activation activity of AaWRKY9 is increased.
Taken together, our results reveal a novel molecular mechanism underlying AaWRKY9 contributes to light‐mediated and jasmonate‐mediated to regulate the biosynthesis of artemisinin in A. annua. Our study provides new insights into integrating the two signalling pathways to regulate terpene biosynthesis in plants.
Sex and aging influence the human immune system, resulting in disparate responses to infection, autoimmunity, and cancer. However, the impact of sex and aging on the immune system is not yet fully ...elucidated. Using small conditional RNA sequencing, we found that females had a lower percentage of natural killer (NK) cells and a higher percentage of plasma cells in peripheral blood compared with males. Bioinformatics revealed that young females exhibited an overrepresentation of pathways that relate to T and B cell activation. Moreover, cell-cell communication analysis revealed evidence of increased activity of the BAFF/APRIL systems in females. Notably, aging increased the percentage of monocytes and reduced the percentage of naïve T cells in the blood and the number of differentially expressed genes between the sexes. Aged males expressed higher levels of inflammatory genes. Collectively, the results suggest that females have more plasma cells in the circulation and a stronger BAFF/APRIL system, which is consistent with a stronger adaptive immune response. In contrast, males have a higher percentage of NK cells in blood and a higher expression of certain proinflammatory genes. Overall, this work expands our knowledge of sex differences in the immune system in humans.
Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo ...with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtypespecific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
L. is known for its specific product "artemisinin" which is an active ingredient for curing malaria. Artemisinin is secreted and accumulated in the glandular secretory trichomes (GSTs) on
leaves. ...Earlier studies have shown that increasing GST density is effective in increasing artemisinin content. However, the mechanism of GST initiation is not fully understood. To this end, we isolated and characterized an R2R3-MYB gene,
, which is expressed specifically in the GSTs of shoot tips. Overexpression of
in
increased GST density and enhanced the artemisinin content, whereas RNA interference of
resulted in the reduction of GST density and artemisinin content. Additionally, neither overexpression lines nor RNAi lines showed an abnormal phenotype in plant growth and the morphology of GSTs. Our study demonstrates that AaMYB17 is a positive regulator of GSTs' initiation, without influencing the trichome morphology.
Background
COVID‐19 is currently a global pandemic, but the response of human immune system to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection remains unclear. Noncoding RNAs ...serve as immune regulators and thus may play a critical role in disease progression.
Methods
We performed multi‐transcriptome sequencing of both noncoding RNAs and mRNAs isolated from the red blood cell depleted whole blood of moderate and severe COVID‐19 patients. The functions of noncoding RNAs were validated by analyses of the expression of downstream mRNAs. We further utilized the single‐cell RNA‐seq data of COVID‐19 patients from Wilk et al. and Chua et al. to characterize noncoding RNA functions in different cell types.
Results
We defined four types of microRNAs with different expression tendencies that could serve as biomarkers for COVID‐19 progress. We also identified miR‐146a‐5p, miR‐21‐5p, miR‐142‐3p, and miR‐15b‐5p as potential contributors to the disease pathogenesis, possibly serving as biomarkers of severe COVID‐19 and as candidate therapeutic targets. In addition, the transcriptome profiles consistently suggested hyperactivation of the immune response, loss of T‐cell function, and immune dysregulation in severe patients.
Conclusions
Collectively, these findings provide a comprehensive view of the noncoding and coding transcriptional landscape of peripheral immune cells during COVID‐19, furthering our understanding and offering novel insights into COVID‐19 pathogenesis.
Highlight
1. miR‐146a‐5p, miR‐21‐5p, and miR‐142‐3p are potential biomarkers of, and therapeutic targets for COVID‐19.
2. Several miRNAs, such as miR‐15b‐5p, are specific for severe COVID‐19 and may serve as potential biomarkers and therapeutic targets.
3. The blood transcriptome profiles suggest hyperactivation of the immune response, loss of T‐cell function, and immune dysregulation in patients with severe COVID‐19.
Abstract
Uveitis is a severe autoimmune disease, and a common cause of blindness; however, its individual cellular dynamics and pathogenic mechanism remain poorly understood. Herein, by performing ...single-cell RNA sequencing (scRNA-seq) on experimental autoimmune uveitis (EAU), we identify disease-associated alterations in cell composition and transcriptional regulation as the disease progressed, as well as a disease-related molecule, PIM1. Inhibiting PIM1 reduces the Th17 cell proportion and increases the Treg cell proportion, likely due to regulation of PIM1 to the protein kinase B (AKT)/Forkhead box O1 (FOXO1) pathway. Moreover, inhibiting PIM1 reduces Th17 cell pathogenicity and reduces plasma cell differentiation. Importantly, the upregulation of PIM1 in CD4
+
T cells and plasma cells is conserved in a human uveitis, Vogt-Koyanagi-Harada disease (VKH), and inhibition of PIM1 reduces CD4
+
T and B cell expansion. Collectively, a dynamic immune cellular atlas during uveitis is developed and implicate that PIM1 may be a potential therapeutic target for VKH.
In diabetic retinopathy (DR), hypoxia-inducible factor (HIF-1α) induces oxidative stress by upregulating glycolysis. This process leads to neurodegeneration, particularly photoreceptor cell damage, ...which further contributes to retinal microvascular deterioration. Further, the regulation of Wnt-inhibitory factor 1 (WIF1), a secreted Wnt signaling antagonist, has not been fully characterized in neurodegenerative eye diseases. We aimed to explore the impact of WIF1 on photoreceptor function within the context of DR.
Twelve-week-old C57BL/KsJ-db/db mice were intravitreally injected with WIF1 overexpression lentivirus. After 4 weeks, optical coherence tomography (OCT), transmission electron microscopy (TEM), H&E staining, and electroretinography (ERG) were used to assess the retinal tissue and function. The potential mechanism of action of WIF1 in photoreceptor cells was explored using single-cell RNA sequencing. Under high-glucose conditions, 661 W cells were used as an in vitro DR model. WIF1-mediated signaling pathway components were assessed using quantitative real-time PCR, immunostaining, and western blotting.
Typical diabetic manifestations were observed in db/db mice. Notably, the expression of WIF1 was decreased at the mRNA and protein levels. These pathological manifestations and visual function improved after WIF1 overexpression in db/db mice. TEM demonstrated that WIF1 restored damaged mitochondria, the Golgi apparatus, and photoreceptor outer segments. Moreover, ERG indicated the recovery of a-wave potential amplitude. Single-cell RNA sequencing and in vitro experiments suggested that WIF1 overexpression prevented the expression of glycolytic enzymes and lactate production by inhibiting the canonical Wnt signaling pathway, HIF-1α, and Glut1, thereby reducing retinal and cellular reactive oxygen species levels and maintaining 661 W cell viability.
WIF1 exerts an inhibitory effect on the Wnt/β-catenin-HIF-1α-Glut1 glycolytic pathway, thereby alleviating oxidative stress levels and mitigating pathological structural characteristics in retinal photoreceptor cells. This mechanism helps preserve the function of photoreceptor cells in DR and indicates that WIF1 holds promise as a potential therapeutic candidate for DR and other neurodegenerative ocular disorders.
Interleukin (IL)-38, a newly discovered IL-1 family cytokine, is expressed in several tissues and secreted by various cells. IL-38 has recently been reported to exert an anti-inflammatory function by ...binding to several receptors, including interleukin-36 receptor (IL-36R), interleukin-1 receptor accessory protein-like 1 (IL-1RAPL1), and interleukin-1 receptor 1 (IL-1R1) to block binding with other pro-inflammatory cytokines and inhibit subsequent signaling pathways; thereby regulating the differentiation and function of T cells, peripheral blood mononuclear cells, macrophages, and dendritic cells. Inflammatory autoimmune diseases, which are common immune-mediated inflammatory syndromes, are characterized by an imbalance between T helper cells (Ths), especially Th1s and Th17s, and regulatory T cells (Tregs). Recent findings have shown that abnormal expression of IL-38 in inflammatory autoimmune diseases, such as rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, primary Sjogren's syndrome, psoriasis, inflammatory bowel disease, hidradenitis suppurativa, ankylosing spondylitis, and glaucoma, involves Th1s, Th17s, and Tregs. In this review, the expression, regulation, and biological function of IL-38 are discussed, as are the roles of IL-38 in various inflammatory autoimmune disorders. Current data support that the IL-38/IL-36R and/or IL-38/IL-1RAPL1 axis primarily play an anti-inflammatory role in the development and resolution of inflammatory autoimmune diseases and indicate a possible therapeutic benefit of IL-38 in these diseases.
Poor sleep has become an important public health issue. With loss of sleep durations, poor sleep has been linked to the increased risks for diseases. Here we employed mass cytometry and single-cell ...RNA sequencing to obtain a comprehensive human immune cells landscape in the context of poor sleep, which was analyzed in the context of subset composition, gene signatures, enriched pathways, transcriptional regulatory networks, and intercellular interactions. Participants subjected to staying up had increased T and plasma cell frequency, along with upregulated autoimmune-related markers and pathways in CD4
T and B cells. Additionally, staying up reduced the differentiation and immune activity of cytotoxic cells, indicative of a predisposition to infection and tumor development. Finally, staying up influenced myeloid subsets distribution and induced inflammation development and cellular senescence. These findings could potentially give high-dimensional and advanced insights for understanding the cellular and molecular mechanisms of pathologic conditions related to poor sleep.
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