Publications by authors named "I Aramburu"
Peptidylarginine deiminase IV (PADI4, PAD4) deregulation promotes the development of autoimmunity, cancer, atherosclerosis and age-related tissue fibrosis. PADI4 additionally mediates immune responses and cellular reprogramming, although the full extent of its physiological roles is unexplored. Despite detailed molecular knowledge of PADI4 activation in vitro, we lack understanding of its regulation within cells, largely due to a lack of appropriate systems and tools.
View Article and Find Full Text PDFBackground: Prinflammatory extracellular chromatin from neutrophil extracellular traps (NETs) and other cellular sources is found in COVID-19 patients and may promote pathology. We determined whether pulmonary administration of the endonuclease dornase alfa reduced systemic inflammation by clearing extracellular chromatin.
Methods: Eligible patients were randomized (3:1) to the best available care including dexamethasone (R-BAC) or to BAC with twice-daily nebulized dornase alfa (R-BAC + DA) for seven days or until discharge.
Somatic mutations commonly occur in hematopoietic stem cells (HSCs). Some mutant clones outgrow through clonal hematopoiesis (CH) and produce mutated immune progenies shaping host immunity. Individuals with CH are asymptomatic but have an increased risk of developing leukemia, cardiovascular and pulmonary inflammatory diseases, and severe infections.
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- Increased levels and variety of human endogenous retrovirus (HERV) transcription are found in many cancer types and are associated with disease outcomes, although the mechanisms are not fully understood.
- The study identified that higher transcription of HERVH in lung squamous cell carcinoma (LUSC) is linked to patient survival and is driven by a CALB1 isoform influenced by HERVH, which begins to express in early preinvasive stages.
- While calbindin (the protein encoded by CALB1) promotes growth in LUSC, its absence triggers cellular senescence and affects the cancer environment by altering the secretion of factors like CXCL8, leading to increased neutrophil presence and poorer patient prognosis in advanced tumors
The factors that influence survival during severe infection are unclear. Extracellular chromatin drives pathology, but the mechanisms enabling its accumulation remain elusive. Here, we show that in murine sepsis models, splenocyte death interferes with chromatin clearance through the release of the DNase I inhibitor actin.
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