Biology subjects

Wilfong, E. M.

Publications and source records attributed to Wilfong, E. M..

4 recordsLinked to original sources

bioRxiv2025

T-cell Multiomic Analysis Identifies Subsets and Mechanisms of Interaction with Epithelial Cells in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by progressive scarring and respiratory failure, with a median survival of 3-5 years. While T-cell numbers are elevated in IPF lungs, their contributions to fibrosis beyond inflammation remain poorly understood. Here, we performed multiplex imaging and single-cell RNA and protein profiling on [~]90,000 CD3 T-cells from control and fibrotic lungs, revealing eleven distinct subsets of CD4 and CD8 T-cells. Among these, we identified a rare CD56 regulatory T-cell subset that is highly activated in fibrosis and exhibits a sustained immunosuppressive phenotype. CXCR4/MIF signaling emerged as a central axis mediating T-cell-epithelial interactions, while epidermal growth factor receptor (EGFR) and TGF{beta} pathways dominated in multiple T-cell subsets. Our findings demonstrate that T-cells in IPF adopt nonclassical activation patterns, driven by epithelial interactions and the fibrotic microenvironment. These studies provide a foundation for exploring novel therapeutic strategies in IPF lungs by modulating T-cell behavior and communication networks.

immunology↗

bioRxiv2025

Metabolic Adaptations Rewire CD4 T Cells in a Subset-Specific Manner in Human Critical Illness with and without Sepsis

Host immunity in sepsis has features of hyperinflammation together with progressive immunosuppression, particularly among CD4 T cells, that can predispose to secondary infections and ineffectual organ recovery. Metabolic and immunologic dysfunction are archetypal findings in critically ill patients with sepsis, but whether these factors are mechanistically linked remains incompletely defined. We characterized functional metabolic properties of human CD4 T cells from critically ill patients with and without sepsis and healthy adults. CD4 T cells in critical illness showed increased subset-specific metabolic plasticity, with regulatory T cells (Tregs) acquiring glycolytic capacity that stabilized suppressive markers FOXP3 and TIGIT and correlated with clinical illness severity. Single-cell transcriptomics identified differential kynurenine metabolism in Tregs, which was validated ex vivo as a mechanism of Treg glycolytic adaptation and suppressive rewiring. These findings underscore immunometabolic dysfunction as a driver of CD4 T cell remodeling in sepsis and suggest therapeutic avenues to restore an effective immune response.

immunology↗

bioRxiv2023

Distinct blood CD3+ CD14+ T Cell-Monocyte complexes harbor HIV and are dynamic, glucose-dependent, and increased in individuals with glucose intolerance

An increased risk of cardiometabolic disease accompanies persistent systemic inflammation. Yet, the innate and adaptive immune system features in persons who develop these conditions remain poorly defined. Doublets, or cell-cell complexes, are routinely eliminated from flow cytometric and other immune phenotyping analyses, which limits our understanding of their relationship to disease states. Using well-characterized clinical cohorts, including participants with controlled HIV as a model for chronic inflammation and increased immune cell interactions, we show that circulating CD14+ monocytes complexed to CD3+ T cells are dynamic, biologically relevant, and increased in individuals with diabetes after adjusting for confounding factors. The complexes form functional immune synapses with increased expression of proinflammatory cytokines and greater glucose utilization. Furthermore, in persons with HIV, the CD3+T-cell: CD14+monocyte complexes had more HIV copies compared to matched CD14+ monocytes or CD4+ T cells alone. Our results demonstrate that circulating CD3+T-cell:CD14+monocyte pairs represent dynamic cellular interactions that may contribute to inflammation and cardiometabolic disease pathogenesis and may originate or be maintained, in part, by chronic viral infections. These findings provide a foundation for future studies investigating mechanisms linking T cell-monocyte cell-cell complexes to developing immune-mediated diseases, including HIV and diabetes. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=127 SRC="FIGDIR/small/538020v2_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@fdc324org.highwire.dtl.DTLVardef@168fc4org.highwire.dtl.DTLVardef@138a9a0org.highwire.dtl.DTLVardef@1087108_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LICirculating CD3+ CD14+ T cell-monocyte complexes are higher in individuals with diabetes. C_LIO_LICD3+ CD14+ T cell-monocytes complexes comprise a heterogenous group of functional and dynamic cell-cell interactions. C_LIO_LIThe proportion of CD3+ CD14+ T cell-monocyte complexes is positively associated with fasting blood glucose and negatively with plasma IL-10 levels and CD4+ T regulatory cells. C_LIO_LICD3+ CD14+ T cell-monocyte complexes are metabolically flexible and can utilize both glycolysis and oxidative phosphorylation for their energy requirements. C_LIO_LIIn persons with treated HIV, CD3+ CD14+ T cell-monocytes have more detectable HIV DNA than circulating CD4+ T cells alone. C_LI

immunology↗

bioRxiv2021

Single-Cell Profiling of the Antigen-Specific Response to BNT162b2 SARS-CoV-2 RNA Vaccine

RNA-based vaccines against SARS-CoV-2 are critical to limiting COVID-19 severity and spread. Cellular mechanisms driving antigen-specific responses to these vaccines, however, remain uncertain. We used single-cell technologies to identify and characterized antigen-specific cells and antibody responses to the RNA vaccine BNT162b2 in longitudinal samples from a cohort of healthy donors. Mass cytometry and machine learning pinpointed a novel expanding, population of antigen-specific non-canonical memory CD4+ and CD8+ T cells. B cell sequencing suggested progression from IgM, with apparent cross-reactivity to endemic coronaviruses, to SARS-CoV-2-specific IgA and IgG memory B cells and plasmablasts. Responding lymphocyte populations correlated with eventual SARS-CoV-2 IgG and a donor lacking these cell populations failed to sustain SARS-CoV-2-specific antibodies and experienced breakthrough infection. These integrated proteomic and genomic platforms reveal an antigen-specific cellular basis of RNA vaccine-based immunity. ONE SENTENCE SUMMARYSingle-cell profiling reveals the cellular basis of the antigen-specific response to the BNT162b2 SARS-CoV-2 RNA vaccine.

immunology↗