Anaphylactic reactions are triggered when allergens enter the blood circulation and activate immunoglobulin E (IgE)-sensitized mast cells (MCs), causing systemic discharge of prestored proinflammatory mediators. As MCs are extravascular, how they perceive circulating allergens remains a conundrum. Here, we describe the existence of a CD301b perivascular dendritic cell (DC) subset that continuously samples blood and relays antigens to neighboring MCs, which vigorously degranulate and trigger anaphylaxis. DC antigen transfer involves the active discharge of surface-associated antigens on 0.5- to 1.0-micrometer microvesicles (MVs) generated by vacuolar protein sorting 4 (VPS4). Antigen sharing by DCs is not limited to MCs, as neighboring DCs also acquire antigen-bearing MVs. This capacity of DCs to distribute antigen-bearing MVs to various immune cells in the perivascular space potentiates inflammatory and immune responses to blood-borne antigens.
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http://dx.doi.org/10.1126/science.aao0666 | DOI Listing |
Cardiol Rev
December 2024
From the Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX.
Salt-sensitive blood pressure is a clinical phenotype defined as exaggerated blood pressure responses to salt loading and salt depletion. This characteristic occurs in 25% of the general population and 50% of patients with hypertension and contributes to the pathogenesis of hypertension in some patients. Hypertension is associated with chronic inflammatory responses and has immune cell accumulation in several hypertensive target organs, including the brain, kidneys, heart, blood vessels, and the perivascular adipose tissue, and these cellular responses likely exacerbate hypertension.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
November 2024
Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil.
Galectin-3 is an endogenous lectin which binds mainly to β-galactosides on the cell surface and extracellular matrix (ECM) glycoproteins. In the thymus, this lectin is constitutively expressed, being involved in thymocyte adhesion, migration, and death. Galectin-3 has been related to type 1 diabetes, an autoimmune disease characterized by pancreatic β-cell destruction mediated by autoreactive T lymphocytes.
View Article and Find Full Text PDFViral mimicry refers to the activation of innate anti-viral immune responses due to the induction of endogenous retroelement (RE) expression. Viral mimicry has been previously described to augment anti-tumor immune responses and sensitize solid tumors to immunotherapy including colorectal cancer, melanoma, and clear renal cell carcinoma. Here, we found that targeting a novel, master epigenetic regulator, Zinc Finger Protein 638 (ZNF638), induces viral mimicry in glioblastoma (GBM) preclinical models and potentiates immune checkpoint inhibition (ICI).
View Article and Find Full Text PDFFront Microbiol
October 2024
Department of Biology, College of Arts and Sciences, Georgia State University, Atlanta, GA, United States.
Owing to their continuous evolution, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) display disparate pathogenicity in mouse models. Omicron and its sublineages have been dominant worldwide. Compared to pre-Omicron VOCs, early Omicron subvariants reportedly cause attenuated disease in human ACE-2-expressing mice (K18-hACE-2).
View Article and Find Full Text PDFbioRxiv
September 2024
Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia and the University of Pennsylvania, PA.
Castleman disease (CD) is inflammatory lymphoproliferative disorder of unclear etiology. To determine the cellular and molecular basis of CD, we analyzed the spatial proteome of 4,485,009 single cells, transcriptome of 50,117 single nuclei, immune repertoire of 8187 single nuclei, and pathogenic mutations in Unicentric CD, idiopathic Multicentric CD, HHV8-associated MCD, and reactive lymph nodes. CD was characterized by increased non-lymphoid and stromal cells that formed unique microenvironments where they interacted with lymphoid cells.
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