Biology subjects

Pezant, N.

Publications and source records attributed to Pezant, N..

3 recordsLinked to original sources

bioRxiv2026

Ancestry-specific rewiring of BCR-MAPK signaling in sarcoidosis B cells

Sarcoidosis is a heterogenous disease of unknown etiology characterized by non-caseating granulomas. Disease prevalence and presentation vary significantly by ancestry and ranges from acute, self-resolving disease to severe, chronic disease. Following previous reports suggesting B cells in the development and pathogenesis of sarcoidosis, we present here results of single-cell RNA sequencing, supporting B cell involvement in sarcoidosis through altered immediate early response, rewiring of MAPK signaling, and ancestry-specific preferential expansion of B cell receptors. Peripheral blood mononuclear cells were obtained from individuals of African or European Ancestry (AA and EA, respectively) including 48 healthy controls, 59 sarcoidosis patients, and 28 systemic lupus erythematosus (SLE) patients. SLE samples were used as a disease control. Differential expression analysis highlighted many differentially expressed genes (DEGs) with almost 5x more in the AA sarcoidosis versus AA control group compared to the EA sarcoidosis versus EA control group. B cells had the most DEGs of all cell types and expression patterns were similar between ancestries, however, sarcoidosis had an opposite transcription pattern than SLE, demonstrating an alternative immune response to acute activation than that seen in a prototypical autoinflammatory disease. This trend was maintained when examining specialized B cell subsets, with the most pronounced effect in the AA sarcoidosis versus AA control comparison. Our results strongly support further investigation of the role of humoral immune response in sarcoidosis and the potential to highlight patient groups likely to benefit from existing B cell therapies.

immunology↗

bioRxiv2026

A KETOGENIC DIET PROMOTES BLOOD-SPINAL CORD BARRIER RESEALING AND PHENOTYPIC SWITCHING OF PRO-INFLAMMATORY MYELOID CELL INFILTRATES IN A PRECLINICAL MODEL OF MULTIPLE SCLEROSIS.

We previously reported that a medium chain triglyceride and{omega} -3 fatty acid enriched ketogenic diet (KD) restored vision and motor functions to mice undergoing experimental autoimmune encephalomyelitis (EAE), a preclinical model of multiple sclerosis (MS). In the mechanistic studies reported here we show that the KD dramatically reduces the infiltration of CD45HI immune cells into the spinal cords of EAE mice when initiated at symptom onset and fed for 2 weeks. Two mechanisms contributed to this reduced accumulation of infiltrates. First, the KD accelerated resealing of the blood-SC barrier (BSCB) in both sexes. This resealing accompanied motor score functional recovery and occurred whether KD feeding was initiated the day of symptom onset or 1 week after symptom onset. Consistent with this resealing, the KD reduced SC levels of soluble IL-1{beta}, a primary cytokine associated with compromising the integrity of CNS-blood barriers. A second mechanism was that the KD increased the percentage of spinal cord infiltrates undergoing apoptosis. Beyond reducing the total abundances of immune cell infiltrates by these two mechanisms, the KD also preserved subpopulations of neutrophils and non-classical mono/macs expressing surface markers associated with inflammation resolution, healing, and tissue repair. Studies leveraging global knockout mouse strains showed unexpectedly that the efficacy of the KD in this interventional paradigm was independent of both the hydroxycarboxylic acid receptor 2 (HCA2) and the anti-stress transcription factor, Nrf2. Collectively, this work advances novel insights by which a KD ameliorates autoimmune-mediated MS-like pathologies to promote functional recovery and more broadly, implies that this dietary strategy has potential benefit for facilitating the healing of disrupted blood-CNS barriers and resolving inflammation in multiple neurodegenerative diseases.

immunology↗

bioRxiv2025

Persistent CD4+ T cell functional deficits during recovery from prolonged symptomatic SARS-CoV-2 infection

Symptoms of acute SARS-CoV-2 infection often resolve quickly but are sometimes associated with persistent immune dysfunction. The factors that predispose individuals to compromised immune function have not been well defined. We investigated CD4+ T cell phenotype and function in a small cohort of individuals who recovered from mild to moderate SARS-CoV-2 infection without hospitalization and were divided into short or prolonged symptom duration groups. Five individuals with prolonged symptom duration showed marked downregulation of CD4 on CD3+CD8- T cells (CD4low group) and a poor response to TCR stimulation with the superantigen Staphylococcal enterotoxin B (SEB), as shown by weak upregulation of the activation markers CD134 and CD69. CD4 surface intensities recovered to normal levels in four of these individuals within 3-12 months. Selected cytokines (IL-1RA, IL-7, and VEGF) were elevated in individuals with low CD4, but plasma levels of anti-S1 IgG did not correlate with CD4 defects. Bulk RNA sequencing of unstimulated and SEB-treated CD3+CD8- T cells revealed a >50% reduction in the number of differentially expressed genes in the CD4low group compared to the same individuals after CD4 levels were recovered and a healthy control group. Upstream regulator analysis of differentially expressed genes in unstimulated CD4low cells suggested a response to IFN, while SEB-stimulated CD4low cells showed reduced functionality of IL-2, CD28, and SATB1 regulated pathways. In summary, prolonged symptomatic recovery from SARS-CoV-2 infection was associated with a global CD4+ T cell response defect, defined by low surface CD4 expression, evidence of IFN signaling, and defective T cell activation.

immunology↗