Biology subjects

Noval Rivas, M.

Publications and source records attributed to Noval Rivas, M..

4 recordsLinked to original sources

bioRxiv2026

Spatial profiling of Kawasaki disease cardiac inflammation identifies STING as a therapeutic target

The cellular subsets and in situ mechanisms underlying the development of coronary arteritis in Kawasaki disease (KD), the leading cause of acquired heart disease in children, remain poorly defined. We characterized the cellular composition and spatial organization of cardiac inflammation in autopsy coronary artery (CA) specimens from KD patients using 64-plex immunofluorescence. We identified spatially organized immune infiltrates of neutrophils, macrophages, and T cells associated with arterial wall destruction and remodeling, as well as disrupted stromal/muscle cell colocalization and diffuse myocardial inflammation. Spatial analysis also revealed expression of the innate immune sensor STING in myeloid cells in KD CA tissues. Pharmacological and genetic inhibition of STING reduced vasculitis development in a mouse model of KD. These findings define the spatial immune architecture of KD cardiac inflammation, reveal inflammatory injury beyond the coronary arteries, and identify STING as a potential therapeutic target for treatment-resistant or severe KD.

immunology↗

bioRxiv2025

Sirtuin 1 Activation Mitigates Murine Vasculitis Severity by Promoting Autophagy and Mitophagy

BACKGROUNDSirtuin 1 (SIRT1), a NAD+-dependent protein deacetylase, regulates cardiovascular inflammation by modulating cellular stress, inhibiting NLRP3 activation, and promoting the clearance of damaged mitochondria. However, its precise role in the pathogenesis of Kawasaki disease (KD), a pediatric systemic vasculitis and the leading cause of acquired heart disease in children, remains unclear. METHODSUsing the Lactobacillus casei cell wall extract (LCWE) murine model of KD, we evaluated the severity of vasculitis in mice supplemented with NAD+ precursors, as well as transgenic mice overexpressing SIRT1, and mice with specific deletion of Sirt1 in vascular smooth muscle cells (VSMCs) and myeloid cells. Proteomics analysis was performed on the abdominal aortas of WT and SIRT1-overexpressing mice. We performed immunofluorescent staining of cardiovascular tissues to assess the expression of proteins related to the autophagy/mitophagy pathway and the pathogenic switch of VSMCs. Western blot analysis was performed on primary VSMCs and cardiovascular tissues to determine the impact of SIRT1 on autophagic flux. The production of pro-inflammatory cytokines was measured in bone marrow-derived macrophages and peritoneal lavage of transgenic mice using ELISAs. RESULTSSIRT1 expression was downregulated in cardiovascular lesions of LCWE-injected mice, which was associated with a significant reduction of circulating levels of nicotinamide. Supplementation of mice with NAD+ precursors or genetic overexpression of SIRT1 significantly reduced the development of LCWE-induced KD, while the specific deletion of Sirt1 in VSMCs or myeloid cells exacerbated vasculitis. Proteomics analysis indicated impaired mitophagy/autophagy and the pathogenic synthetic switch of VSMCs in LCWE-injected mice, which was rescued with SIRT1 overexpression and associated with reduced production of proinflammatory cytokines. CONCLUSIONSThis study reveals the presence of an impaired NAD+-SIRT1 axis in the pathogenesis of LCWE-induced KD vasculitis and the therapeutic potential of targeting this axis to reduce cardiovascular lesions and inflammation.

immunology↗

bioRxiv2020

A monoclonal antibody against staphylococcal enterotoxin B superantigen inhibits SARS-CoV-2 entry in vitro

We recently discovered a superantigen-like motif, similar to Staphylococcal enterotoxin B (SEB), near the S1/S2 cleavage site of SARS-CoV-2 Spike protein, which might explain the multisystem-inflammatory syndrome (MIS-C) observed in children and cytokine storm in severe COVID-19 patients. We show here that an anti-SEB monoclonal antibody (mAb), 6D3, can bind this viral motif, and in particular its PRRA insert, to inhibit infection by blocking the access of host cell proteases, TMPRSS2 or furin, to the cleavage site. The high affinity of 6D3 for the furin-cleavage site originates from a poly-acidic segment at its heavy chain CDR2, a feature shared with SARS-CoV-2-neutralizing mAb 4A8. The affinity of 6D3 and 4A8 for this site points to their potential utility as therapeutics for treating COVID-19, MIS-C, or common cold caused by human coronaviruses (HCoVs) that possess a furin-like cleavage site.

immunology↗

bioRxiv2020

Identification of a unique TCR repertoire, consistent with a superantigen selection process in Children with Multi-system Inflammatory Syndrome

Multisystem Inflammatory Syndrome in Children (MIS-C), a hyperinflammatory syndrome associated with SARS-CoV-2 infection, shares many clinical features with toxic shock syndrome, which is triggered by bacterial superantigens. The superantigen specificity for binding different V{beta}-chains results in V{beta}-skewing, whereby T cells with specific V{beta}-chains and diverse antigen specificity are overrepresented in the TCR repertoire. Here, we characterized the TCR repertoire of MIS-C patients and found a profound expansion of TCR Beta Variable gene (TRBV)11-2. Furthermore, TRBV11-2 skewing was remarkably correlated with MIS-C severity and serum cytokine levels. Further analysis of TRBJ gene usage and CDR3 length distribution of MIS-C expanding TRBV11-2 clones revealed extensive junctional diversity, indicating a superantigen-mediated selection process for TRBV expansion. In silico modelling indicates that polyacidic residues in TCR V{beta}11-2 engage in strong interactions with the superantigen-like motif of SARS-CoV-2 spike glycoprotein. Overall, our data indicate that the immune response in MIS-C is consistent with superantigenic activation. HighlightsO_LIMultisystem Inflammatory Disease in Children (MIS-C) patients exhibit T cell receptor (TCR) repertoire skewing, with expansion of T cell Receptor Beta Variable gene (TRBV)11-2 C_LIO_LITRBV11-2 skewing correlates with MIS-C severity and cytokine storm C_LIO_LIJ gene/CDR3 diversity in MIS-C patients is compatible with a superantigen selection process C_LIO_LIIn silico modelling indicates TCR V{beta}11-2 engages in CDR3-independent interactions with the polybasic insert P681RRAR in the SAg-like motif of SARS-CoV-2 spike C_LI

immunology↗