Biology subjects

Arun, N.

Publications and source records attributed to Arun, N..

4 recordsLinked to original sources

bioRxiv2026

Lymphatic CD49a is a driver of meningeal immune aging and cognitive decline.

Aging is associated with progressive accumulation and dysregulation of dural immune cells, coinciding with impaired CSF drainage and lymphatic function. Prior work has shown that improving lymphatic function in aged mice is sufficient to ameliorate age-associated cognitive decline, and that local immune cells can directly regulate lymphatic draining function. Yet, the endothelial-intrinsic mechanisms driving lymphatic dysfunction remain unclear. Here we found that the integrin CD49a is upregulated in aged lymphatic endothelial cells and regulates CCL21 release. Accordingly, genetic deletion of CD49a in lymphatic endothelial cells broadly reverses age-associated immune dysfunction across dural myeloid, lymphoid and dendritic cell compartments, limits glial aging, and mitigates cognitive and social behavioral deficits, thereby revealing a targetable endothelial-intrinsic mechanism of lymphatic aging.

neuroscience↗

bioRxiv2026

A Single-Cell Atlas of the Mouse Dural Meninges Reveals Pervasive Sex Differences Across Cellular Compartments

The dural compartment of the meninges forms a dynamic interface between the brain and the periphery, hosting diverse immune, vascular, mural and fibroblast populations. Single-cell studies have begun charting meningeal cellular diversity, yet a comprehensive view encompassing all major cellular compartments, intercellular communication, and the influence of sex remains lacking. Here, we present a single-cell transcriptomic atlas of the adult mouse dural meninges, profiling all major cell types in male and female mice at steady state. We uncover broad sex differences in cell-type-specific proportion, transcriptional programs, intercellular communication, and disease relevant signatures. Histological and cytometry analyses validate the biological relevance of these findings, establishing this atlas as a foundation for studying meningeal contributions to neurological disease in a sex-aware manner.

neuroscience↗

bioRxiv2025

MAIT cell responses to intracellular and extracellular pathogens are mediated by distinct antigen presenting cells

Mucosal-associated invariant T (MAIT) cells recognize microbial derivatives of riboflavin synthesis presented by the MHC class I-related (MR1) molecule. Although these metabolites are highly conserved among bacteria, the cells that present them remain unknown. Here, we show type-17 MAIT cells respond to diverse isolates of the extracellular pathogen Acinetobacter baumannii and promote bacterial clearance. Both hematopoietic and non-hematopoietic cells mediate MR1 presentation within the lungs and mediastinal lymph nodes (meLNs). Conversely, the type-1 MAIT cell response to the intracellular pathogen Francisella tularensis requires MR1 presentation by type-2 conventional dendritic cells (cDC2s) within meLNs and ablation of these cells or their expression of MR1 renders animals more susceptible to the infection. Although MR1 is broadly expressed at homeostasis, A. baumannii enhances MR1 on macrophages and fibroblasts, while F. tularensis increases expression on cDC2s. These results demonstrate that microbial tropism dictates which APCs mediate MR1 presentation of metabolites, revealing alternative therapeutic approaches.

immunology↗

bioRxiv2024

Monocyte to macrophage differentiation and changes in cellular redox homeostasis promote cell type-specific HIV latency reactivation

Human Immunodeficiency Virus (HIV) latency regulation in monocytes and macrophages can vary according to signals directing differentiation, polarization, and function. To investigate these processes, we generated an HIV latency model in THP-1 monocytes and showed differential levels of HIV reactivation among clonal populations. Monocyte-to-macrophage differentiation of HIV-infected primary human CD14+ and THP-1 cells induced HIV reactivation and showed that virus production increased concomitant with macrophage differentiation. We applied the HIV-infected THP-1 monocyte-to- macrophage (MLat) model to assess the biological mechanisms regulating HIV latency dynamics during monocyte-to-macrophage differentiation. We pinpointed PKC signaling pathway activation and Cyclin T1 upregulation as inherent differentiation mechanisms that regulate HIV latency reactivation. Macrophage polarization regulated latency, revealing pro-inflammatory M1 macrophages suppressed HIV reactivation while M2 macrophages promoted HIV reactivation. Because macrophages rely on reactive- oxygen species (ROS) to exert numerous cellular functions, we disrupted redox pathways and discovered that inhibitors of the thioredoxin (Trx) system acted as latency promoting agents (LPAs) in T-cells and monocytes, but opposingly acted as latency reversing agents (LRAs) in macrophages. We explored this mechanism with Auranofin, a clinical candidate for reducing HIV reservoirs, and demonstrated Trx reductase (TrxR) inhibition led to ROS induced NF-{kappa}B activity, which promoted HIV reactivation in macrophages, but not in T-cells and monocytes. Collectively, cell type-specific differences in HIV latency regulation could pose a barrier to HIV eradication strategies.

microbiology↗