Several mesenchymal cell populations are known to regulate intestinal stem cell (ISC) self-renewal and differentiation. However, the influences of signaling mediators derived from mesenchymal cells other than ISC niche factors on epithelial homeostasis remain poorly understood. Here, we show that host and microbial metabolites, such as taurine and GABA, act on PDGFRαhigh Foxl1high sub-epithelial mesenchymal cells to regulate their transcription.
View Article and Find Full Text PDFInterstitial pneumonia (IP) is a refractory disease that causes severe inflammation and fibrosis in the interstitium of the lungs, often resulting in the development of lung cancer (LC) during treatment. Previous studies have demonstrated that the prognosis of LC complicated by IP is inferior to that of LC without IP. It is therefore of the utmost importance to gain a deeper understanding of the heterogeneity of such tumors.
View Article and Find Full Text PDFMicropapillary adenocarcinoma (MPC) is an aggressive histological subtype of lung adenocarcinoma (LUAD). MPC is composed of small clusters of cancer cells exhibiting inverted polarity. However, the mechanism underlying its formation is poorly understood.
View Article and Find Full Text PDFMol Ther Methods Clin Dev
December 2024
Cord blood (CB)-derived chimeric antigen receptor (CAR)-natural killer (NK) cells targeting CD19 have been shown to be effective against B cell malignancies. While human CD56 NK cells can be expanded , NK cells can also be differentiated from hematopoietic progenitor cells. It is still unclear whether CAR-NK cells originate from mature NK cells or NK progenitor cells in CB.
View Article and Find Full Text PDFThe growth plate is the primary site of longitudinal bone growth with chondrocytes playing a pivotal role in endochondral bone development. Chondrocytes undergo a series of differentiation steps, resulting in the formation of a unique hierarchical columnar structure comprising round, proliferating, pre-hypertrophic, and hypertrophic chondrocytes. Pre-hypertrophic chondrocytes, which exist in the transitional stage between proliferating and hypertrophic stages, are a critical cell population in the growth plate.
View Article and Find Full Text PDFExperimental autoimmune encephalomyelitis (EAE) is the most widely used rodent model for multiple sclerosis. Interferon-γ (IFN-γ) and regulatory T cells (Tregs) are individually well known to play beneficial roles in amelioration of EAE. However, little is known about the relationship between IFN-γ and Tregs during the disease.
View Article and Find Full Text PDFExacerbation of scarring can originate from a minority fibroblast population that has undergone inflammatory-mediated genetic changes within the wound microenvironment. The fundamental relationship between molecular and spatial organization of the repair process at the single-cell level remains unclear. We have developed a novel, high-resolution spatial multiomics method that integrates spatial transcriptomics with scRNA-Seq; we identified new characteristic features of cell-cell communication and signaling during the repair process.
View Article and Find Full Text PDFOne of the dense granule proteins named GRA15 in Toxoplasma gondii (T. gondii), is known to support an innate immune response in host through activation of NF-κB. However, little is known about advantages of GRA15 for parasites.
View Article and Find Full Text PDFThe intestinal lumen is rich in gut microbial metabolites that serve as signaling molecules for gut immune cells. G-protein-coupled receptors (GPCRs) sense metabolites and can act as key mediators that translate gut luminal signals into host immune responses. However, the impacts of gut microbe-GPCR interactions on human physiology have not been fully elucidated.
View Article and Find Full Text PDFWhereas severe COVID-19 is often associated with elevated autoantibody titers, the underlying mechanism behind their generation has remained unclear. Here we report clonal composition and diversity of autoantibodies in humoral response to SARS-CoV-2. Immunoglobulin repertoire analysis and characterization of plasmablast-derived monoclonal antibodies uncovered clonal expansion of plasmablasts producing cardiolipin (CL)-reactive autoantibodies.
View Article and Find Full Text PDFBleomycin (BLM) induces lung injury, leading to inflammation and pulmonary fibrosis. Regulatory T cells (Tregs) maintain self-tolerance and control host immune responses. However, little is known about their involvement in the pathology of pulmonary fibrosis.
View Article and Find Full Text PDFWe previously demonstrated hepatic, cardiac, and skin inflammation in a high-fat diet-induced steatotic liver disease (SLD) model. However, the molecular mechanism in the kidneys in this model remains unclear. It has been recently reported that SGLT2 inhibitors improve chronic kidney disease (CKD).
View Article and Find Full Text PDFDetecting antibodies, particularly those targeting donor human leukocyte antigens in organ transplantation and self-antigens in autoimmune diseases, is crucial for diagnosis and therapy. Radioprotective 105 (RP105), a Toll-like receptor family protein, is expressed in immune-competent cells, such as B cells. Studies in mice have shown that the anti-mouse RP105 antibody strongly activates B cells and triggers an adjuvant effect against viral infections.
View Article and Find Full Text PDFMesothelin (MSLN) is expressed in the mesothelium in normal tissues but is overexpressed in various malignant tumors. In this study, we searched for genes that were more frequently expressed in cases of endometrioid carcinoma (EC) with the MELF (microcystic, elongated, and fragmented) pattern using laser microdissection and RNA sequencing, and found that MSLN was predominantly expressed in cases with the MELF pattern. The role of MSLN in EC was analyzed by generating MSLN-knockout and -knockdown EC cell lines.
View Article and Find Full Text PDFRegulated neural-metabolic-inflammatory responses are essential for maintaining physiological homeostasis. However, the molecular machinery that coordinates neural, metabolic, and inflammatory responses is largely unknown. Here, we show that semaphorin 6D (SEMA6D) coordinates anxiogenic, metabolic, and inflammatory outputs from the amygdala by maintaining synaptic homeostasis.
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