Injury or impaired clearance of apoptotic cells leads to the pathological accumulation of necrotic corpses, which induce an inflammatory response that initiates tissue repair. In addition, antigens present in necrotic cells can sometimes provoke a specific immune response and it has been argued that necrosis could explain adaptive immunity in seemingly infection-free situations, such as after allograft transplantation or in spontaneous and therapy-induced tumour rejection. In the mouse, the CD8alpha+ subset of dendritic cells phagocytoses dead cell remnants and cross-primes CD8+ T cells against cell-associated antigens. Here we show that CD8alpha+ dendritic cells use CLEC9A (also known as DNGR-1), a recently-characterized C-type lectin, to recognize a preformed signal that is exposed on necrotic cells. Loss or blockade of CLEC9A does not impair the uptake of necrotic cell material by CD8+ dendritic cells, but specifically reduces cross-presentation of dead-cell-associated antigens in vitro and decreases the immunogenicity of necrotic cells in vivo. The function of CLEC9A requires a key tyrosine residue in its intracellular tail that allows the recruitment and activation of the tyrosine kinase SYK, which is also essential for cross-presentation of dead-cell-associated antigens. Thus, CLEC9A functions as a SYK-coupled C-type lectin receptor to mediate sensing of necrosis by the principal dendritic-cell subset involved in regulating cross-priming to cell-associated antigens.
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http://dx.doi.org/10.1038/nature07750 | DOI Listing |
Discov Oncol
December 2024
Department of Neurosurgery, West China Hospital of Sichuan University, No. 37, Guoxue Lane, Wuhou District, Chengdu, China.
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View Article and Find Full Text PDFImmunol Res
December 2024
Department of Respiratory Medicine, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China.
This study aims to characterize the majority of immune cell subsets in peripheral blood mononuclear cells in children with Mycoplasma pneumoniae pneumonia (MPP) by a 21-color flow cytometry panel. Patients who met the predetermined eligibility criteria for pneumonia diagnosis were recruited for the research study. Multi-color flow cytometry was conducted on the peripheral blood mononuclear cells of each patient group, which were then subjected to dimensionality reduction and cluster analysis.
View Article and Find Full Text PDFFree Radic Res
December 2024
Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Patients with hypoxemia require high-concentration oxygen therapy. However, prolonged exposure to oxygen concentrations 21% higher than physiological concentrations (hyperoxia) may cause oxidative cellular damage. Pulmonary alveolar epithelial cells are major targets for hyperoxia-induced oxidative stress.
View Article and Find Full Text PDFJ Vis Exp
December 2024
Department of Medical Materials Science & Technology, Institute for Biomedical Engineering, University Hospital Tübingen;
Foreign body reaction (FBR), an immune-mediated complex healing process, plays a crucial role in integrating implants into the body. Macrophages, as the first line of immune system interaction with implant surfaces, play a bidirectional role in modulating the inflammation-regeneration balance. For a deep understanding and the evaluation of the reactions between implant materials and immune responses, reliable in vitro methods and protocols are pivotal.
View Article and Find Full Text PDFClin Exp Rheumatol
December 2024
Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Objectives: Systemic sclerosis (SSc), a chronic autoimmune disorder, characterised by local inflammation and progressive fibrosis. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) has been established as a key mediator in fibrotic processes across multiple organs, primarily through binding to its receptor, fibroblast growth factor-inducible 14 (Fn14). However, the precise role of the TWEAK/Fn14 signalling in SSc pathogenesis remains unclear.
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