Biology subjects

Figueiredo Galvao, H. B.

Publications and source records attributed to Figueiredo Galvao, H. B..

2 recordsLinked to original sources

bioRxiv2026

Immune-Mediated Necrotic Cell Death Initiated by Stressed Cardiomyocytes is a Major Contributor to Cardiomyocyte Loss Following Myocardial Infarction

AimsPercutaneous coronary intervention has improved survival following myocardial infarction, yet strategies to further reduce infarct size are limited. This study investigates the role of cytotoxic {gamma}{delta}-T cells in ischemic cardiomyocyte death and potential therapeutic interventions to reduce infarct size. MethodsGenetic and pharmacological approaches were used to delete {gamma}{delta}-T cells and their specific proteins to assess their involvement in cardiomyocyte death using mouse models of permanent ligation (PL) and ischemia/reperfusion (IR). Results{gamma}{delta}-T cells accumulated in infarct zones within 6h post-PL, expressing IFN-{gamma}, TNF-, granzyme B, and perforin. Their deletion reduced infarct size by 73% (PL) and 64% (IR). They induced cardiomyocyte death via apoptosis, gasdermin E-dependent pyroptosis, and MLKL-dependent necroptosis; {gamma}{delta}-T cell depletion reduced apoptosis by 80% and pyroptosis by 38%, with perforin deletion yielding similar effects. Necroptosis, attributed to combined IFN-{gamma}/TNF- cytotoxicity, decreased by 67%. Cytoplasmic DNA (cDNA) in stressed cardiomyocytes activated the cGAS/STING pathway, inducing expression of chemoattractant MCP-1 and death signal RAE-1. These signals recruited and activated {gamma}{delta}-T cells, which then triggered the death of the stressed cardiomyocytes. STING inhibition suppressed these expressions, reducing {gamma}{delta}-T cell accumulation and infarct size. NKG2D-deficient {gamma}{delta}-T cells prevented activation and reduced infarct size. Administration of an anti-IFNAR antibody at PL onset markedly reduced infarct size. ConclusionEarly activation of cytotoxic {gamma}{delta}-T cells via cardiomyocyte stress signals contributes significantly to immunogenic cardiomyocyte death. Targeting the STING pathway and type I interferon signalling presents a promising therapeutic avenue to mitigate infarct size and improve outcomes.

immunology↗

bioRxiv2025

Marginal zone B cells are antigenically activated, infiltrate the kidneys, and exacerbate angiotensin II-dependent hypertension in mice

AimsB cells contribute to the development of hypertension, yet, the specific B cell subsets involved, the mechanism underlying their activation, and the relevance of these responses to human disease remain poorly defined. Methods and resultsWe used single-cell RNA sequencing, single-cell B cell receptor (BCR) VDJ sequencing, and high dimensional flow cytometry to characterise B cell responses in murine angiotensin II-induced hypertension. Chronic angiotensin II infusion in male and female mice increased systolic blood pressure and selectively expanded marginal zone B (MZB) cells, with evidence of antigen-dependent activation, including clonal BCR expansion, enrichment of IGHV1 B cell receptor variants, and increased expression of activation markers (CD69 and Nur77). Intercellular communication analyses revealed enhanced antigen-presentation signalling between MZB and CD8+ T cells in hypertensive mice. Activated MZB-like memory B cells also accumulated in the kidneys of hypertensive mice. Consistent with these findings, multiomic analysis of kidneys from patients with hypertensive chronic kidney disease (CKD) demonstrated an increase in memory B cells with a MZB phenotype and enrichment of antigen-presentation-linked communication with CD8+ T cells. Importantly, hypertensive responses to angiotensin II infusion were significantly blunted in mice lacking MZB cells (BAFF-R-/-). ConclusionOur findings identify MZB cells as a selectively activated, antigen-responsive B cell subset that amplified pathogenic immune responses in murine and human hypertension. By linking subset-specific BCR activation to immune cross-talk and disease causality, this study identifies MZB cells - and the (auto)antigens that activate them - as promising targets for precision immunomodulatory strategies in hypertension.

physiology↗