Biology subjects

Petrova, T. V.

Publications and source records attributed to Petrova, T. V..

6 recordsLinked to original sources

bioRxiv2026

A Glycosylation-Dependent Checkpoint Restrains Intestinal Intra-Epithelial Lymphocyte Activation

Intraepithelial lymphocytes (IELs) are abundant in the intestinal epithelium, where they maintain barrier integrity and provide immune defense. Because of their potent cytotoxic and effector potential, IEL activity must be tightly controlled to prevent tissue damage. However, the mechanisms that calibrate IEL responsiveness remain unclear. Here, we identify glucosaminyl (N-acetyl) transferase 2 (Gcnt2) as a key restrainer of both natural and induced gut IEL. Among T cells, Gcnt2 is uniquely enriched in the intestine and partly dependent on retinoic acid signaling. GCNT2-mediated branched glycosylation marks IELs with signatures of tissue adaptation and reduced TCR responsiveness. Genetic ablation of Gcnt2 enhanced IEL degranulation, cytokine production, and cytotoxicity upon stimulation, improving bacterial clearance and limiting infection-induced disease, while aggravating the pathological consequences of strong T cell activation. Mechanistically, GCNT2-mediated glycosylation of CD45 reduced its phosphatase activity, thereby dampening TCR signaling and effector responses. Together, these findings reveal GCNT2 as a glycosylation-dependent checkpoint that fine-tunes IEL effector functions, uncovering a novel mechanism by which the intestinal immune system balances responsiveness and tolerance. SummaryGCNT2-mediated I-branching glycosylation of CD45 restrains IEL activation.

immunology↗

bioRxiv2025

Aquaporin-1 sustains lymphangiogenic responses in inflammatory microenvironments

Intestinal lymphatic vessels are essential for dietary lipid absorption and immune cell trafficking. Specialized villus lymphatic capillaries, lacteals, undergo constant VEGF-C-dependent renewal to maintain their function in a hyperosmolar, inflammatory microenvironment exposed to dietary by-products. The mechanisms of lacteal adaptation remain incompletely understood. We integrated new and published single-cell RNA-sequencing data to profile murine small-intestinal lymphatic endothelial cells (LECs) and identified three distinct subsets. Lacteal LECs display a transcriptional signature resembling Ptx3 immune-interacting LECs characterized by high expression of Aqp1, encoding the aquaporin-1 water channel. LEC-specific deletion of Aqp1 reduced lacteal length, impaired lipid uptake, and limited weight gain on a high-fat diet, underscoring the importance of water homeostasis in lacteal maintenance. AQP1 also promoted VEGF-C-dependent LEC migration under osmotic stress and, uniquely, was upregulated during inflammatory remodelling in secondary lymphedema and lymphatic malformations, but not during embryonic lymphangiogenesis. These findings link lacteal regeneration to inflammatory lymphatic remodelling and highlight tissue osmolarity as a key biophysical factor in postnatal lymphangiogenesis.

pathology↗

bioRxiv2025

Multi-omics analysis of endothelial cells reveals the metabolic diversity that underlies endothelial cell functions

Endothelial cells (ECs) line the vascular system and are key players in vascular homeostasis, yet their metabolic diversity across tissues, vascular beds, and growth states remains poorly understood. This study examines metabolic differences between proliferating and quiescent ECs and compares blood and lymphatic endothelium using proteomics and metabolomics. Our findings indicate that metabolism in quiescent ECs is not dormant but reorganized in a cell-specific manner, with decreased heme intermediates in human umbilical vein ECs and increased branched-chain amino acid catabolism across all quiescent ECs. Consistent with the differences identified in the omics data, perturbation studies revealed that inhibiting enzymes involved in heme, glutamate, fatty acid, and nucleotide biosynthesis led to distinct phenotypic responses in blood and lymphatic ECs. These findings highlight the importance of metabolic pathways in sustaining both proliferating and quiescent ECs and reveal how ECs from different vascular beds rely on distinct metabolic processes to maintain their functional states.

systems biology↗

bioRxiv2023

Specialized mesenteric lymphatic capillaries by-pass the mesenteric lymph node chain to transport peritoneal antigens directly into mediastinal lymph nodes.

Lymphatic vessels (LVs) are indispensable for tissue fluid homeostasis and immune cell trafficking. The network of LVs that channel fluids from the gut into mesenteric lymph nodes (MLN) has been recognized as the sole lymphatic system in the mesentery. Here we describe an alternative, functionally autonomous set of capillary mesenteric LVs (capMLVs) that by-pass the MLNs and drain directly into mediastinal LNs. CapMLVs develop perinatally from valves of collective mesenteric lymphatic vessels (colMLVs) in response to arterial endothelial cell-derived VEGF-C. Once extended, capMLVs detach from colMLVs to form an independent elongated network comprised of LYVE1+, CCL21+ endothelial cells. Avascular areas of the mesentery juxtaposed to capMLVs contain cell islets that express ACKR4. This CCL21-scavenging atypical receptor facilitates the migration of mesenteric phagocytes into capMLVs to be channeled directly into mediastinal LNs. This allows peritoneum-derived ominous antigens to be processed separately from alimentary antigens.

developmental biology↗

bioRxiv2021

Mitochondrial genome phylogeny of voles and lemmings (Rodentia: Arvicolinae): evolutionary and taxonomic implications

Arvicolinae is one of the most impressive placental radiations with over 150 extant and numerous extinct species that emerged since the Miocene in the Northern Hemisphere. The phylogeny of Arvicolinae has been studied intensively for several decades using morphological and genetic methods. Here, we sequenced 30 new mitochondrial genomes to better understand the evolutionary relationships among the major tribes and genera within the subfamily. The phylogenetic and molecular dating analyses based on 11,391 bp concatenated alignment of protein-coding mitochondrial genes confirmed the monophyly of the subfamily. While Bayesian analysis provided a high resolution across the entire tree, Maximum Likelihood tree reconstruction showed weak support for the ordering of divergence and interrelationships of tribal level taxa within the most ancient radiation. Both the interrelationships among tribes Lagurini, Ellobiusini and Arvicolini, comprising the largest radiation and the position of the genus Dinaromys within it also remained unresolved. For the first time complex relationships between genus level taxa within the species-rich tribe Arvicolini received full resolution. Particularly Lemmiscus was robustly placed as sister to the snow voles Chionomys in the tribe Arvicolini in contrast with a long-held belief of its affinity with Lagurini. Molecular dating of the origin of Arvicolinae and early divergences obtained from the mitogenome data were consistent with fossil records. The mtDNA estimates for putative ancestors of the most genera within Arvicolini appeared to be much older than it was previously proposed in paleontological studies.

zoology↗

bioRxiv2021

Small Intestinal Resident Eosinophils Maintain Gut Homeostasis Following Microbial Colonisation

Intestinal homeostasis following postnatal microbial colonization requires the coordination of multiple processes including the activation of immune cells, cell-cell communication, the controlled deposition of extracellular matrix, and epithelial cell turnover and differentiation. The intestine harbors the largest frequency of resident eosinophils of all homeostatic organs, yet the functional significance of eosinophil recruitment to this organ has long remained enigmatic. Eosinophils are equipped to both respond to, and modify, their local tissue environment and thus are able to regulate the adaption of tissues to environmental changes. We report a critical role for eosinophils in regulating villous structure, barrier integrity and motility in the small intestine. Notably, the microbiota was identified as a key driver of small intestinal eosinophil activation and function. Collectively our findings demonstrate a critical role for eosinophils in facilitating mutualistic interactions between host and microbiota and provide a rationale for the functional significance of their early life recruitment in the small intestine. HIGHLIGHTSO_LIThe microbiota is a critical regulator of eosinophil activation and turnover C_LIO_LIEosinophils uphold intestinal barrier integrity following microbial colonization C_LIO_LILoss of eosinophils at steady-state results in increased villous blunting and altered intestinal motility C_LI

immunology↗