Biology subjects

Tjitropranoto, A.

Publications and source records attributed to Tjitropranoto, A..

2 recordsLinked to original sources

bioRxiv2025

Single-cell transcriptomics identifies a dampened neutrophil function and accentuated T-cell cytotoxicity in tobacco flavored e-cigarette exposed mouse lungs

E-cigarettes (e-cigs) are a public health concern for young adults due to their rising popularity despite evidence of harmful effects. Yet an extensive study defining the cell-specific immune changes upon exposure to flavored e-cigs remains elusive. To determine the immunological lung landscape upon acute nose-only exposure of C57BL/6J to flavored e-cig aerosols, we performed single-cell RNA sequencing (scRNA seq). Analyses of the levels of metals in the e-cig aerosol generated daily during exposure revealed a flavor-dependent variation in the day-to-day leaching of the levels of metals like Ni, Cu, K and Zn, among others. scRNA profiles of 71,725 cells generated from control and treatment groups (n=2/sex/group) found maximum dysregulation of (a) myeloid cell function in menthol (324 differentially enriched genes (DEG)) and tobacco (553 DEGs) -flavor exposed and (b) lymphoid cell function in fruit (112 DEGs)-flavored e-cig aerosol exposed mouse lungs as compared to air. Flow cytometry analyses identified marked increase in the neutrophil percentage and a decrease in the eosinophil count in menthol and tobacco-flavored e-cig aerosol exposed mouse lungs which corroborated with our scRNA seq data. We further found an: (a) increase in CD8+ T cell percentages, (b) upregulation of inflammatory genes like Stat4, Il1bos, Il1b, Il1ra and Cxcl3 and (c) enrichment of terms like T-helper cell 1cytokine function and NK cell degranulation in the lungs of e-cig aerosol exposed mouse when compared to control. Interestingly, the increase in the level of immature neutrophils characterized by Ly6G deficiency and reduction in the S100A8 (marker for neutrophil activation) using immunofluorescence in tobacco-flavored e-cig aerosol exposed mouse lung sections point towards a possible shift in the neutrophil dynamics upon exposure to e-cigs. Overall, this study identifies flavor dependent changes in myeloid and lymphoid-cell mediated responses in the mouse lungs exposed to acute nose-only e-cig aerosols and provides a resource to influence future research in select /specific cell types to understand the immunological implications of long-term use of e-cigs.

pharmacology and toxicology↗

bioRxiv2021

A single-cell reference atlas delineates CD4+ T cell subtype-specific adaptation during acute and chronic viral infections

CD4+ T cells are critical orchestrators of immune responses against a large variety of pathogens, including viruses. The multifaceted roles of CD4+ T cells, including their help to innate cells, CD8+ T and B cells and their support for long-lived immunity rely on a profound functional heterogeneity. While multiple CD4+ T cell subtypes and their key transcriptional regulators have been identified, there is a lack of consistent definition for CD4+ T cell transcriptional states. In addition, the progressive changes affecting CD4+ T cell subtypes during and after immune responses remain poorly defined. Taking advantage of single-cell transcriptomics, efficient computational methods, and robust animal models, we characterize the transcriptional landscape of CD4+ T cells responding to self-resolving and chronic viral infections. We build a comprehensive atlas of virus-specific CD4+ T cells and their evolution over time, and identify six major distinct cell states that are consistently observed in acute and chronic infections. During the course of acute infection, T cell composition progressively changes from effector to memory states, with subtype-specific gene modules and kinetics. Conversely, T cells in persistent infections fail to transition from effector to memory states, and acquire distinct, chronicity-associated transcriptional programs. By single-cell T cell receptor (TCR) sequencing analysis, we characterize the clonal structure of virus-specific CD4+ T cells across individuals and T cell subtypes. We find that virus-specific CD4+ T cell responses are mainly private across individuals and that most T cells differentiate into all subtypes independently of their TCR, in both acute and chronic infections. Finally, we show that our CD4+ T cell atlas can be used as a reference to accurately interpret cell states in external single-cell datasets. Overall, this study describes a previously unappreciated level of adaptation of the transcriptional states of CD4+ T cells responding to viruses and provides a new computational resource for CD4+ T cell analysis, available online at https://spica.unil.ch.

immunology↗