Biology subjects

Schernthanner, M.

Publications and source records attributed to Schernthanner, M..

5 recordsLinked to original sources

bioRxiv2026

Weaning imprints a hybrid cytotoxic-regulatory identity on intestinal CD4+ T lymphocytes

The intestinal immune system must adapt as the neonatal gut shifts from milk to solid food and becomes densely colonized. How the T cell compartment is established under these conditions remains unclear. Using fate-mapping to timestamp naive T cells, with imaging, transcriptomic, and repertoire analyses, we tracked them from suckling to adulthood. Intestinal T cell entry peaked at weaning, coinciding with relocation from crypts to villi guided by the tissue microenvironment and, partly, the microbiota. T cells timestamped at suckling persisted into adulthood and, at weaning, adopted a transient cytotoxic-regulatory state in the lamina propria, with granzyme B expression microbiota-dependent only in the ileum. Clonal expansions at weaning were restricted to the small intestinal lamina propria and absent in germ-free mice. Most expanded clones recognized early-life commensals. Weaning is a physiological window of transient inflammation imprinting a hybrid CD4 T cell compartment, suggesting that early-life commensals modulate T cell selection.

immunology↗

bioRxiv2026

E-cadherin-mediated neighborhood surveillance dictates pre-malignant outcomes

Stratified epithelia accumulate oncogenic mutations throughout life, yet overgrowths are rare. How epithelia detect and eliminate aberrant clones remains poorly understood. Using a mouse model of oncogenic clonal mosaicism in the skin, we find that pre-malignant epidermal cells redistribute E-cadherin to interfaces shared with wild-type neighbors, generating local tension heterogeneity that triggers elimination by cell competition. We show that gain or loss of E-cadherin can each drive competitive elimination, and although mechanical routes differ, both establish tension heterogeneity between neighbors, rather than any absolute adhesion state, as the critical determinant of epidermal fitness. This mechanism carries the seeds of its own failure: these tension differentials precipitate clonal sorting, depleting the wild-type contacts that surveillance requires. Pre-malignant cells then become supercompetitors, eliminating wild-type neighbors and expanding hyperplastically. Mechanical heterogeneity therefore endows tissues with an active, yet inherently fragile error-correction system whose collapse initiates a switch in competitive status, increasing tumorigenesis susceptibility.

cell biology↗

bioRxiv2026

A commensally regulated immune rheostat fine-tunes skin barrier fitness

At the skins surface, the epidermis must balance stem cell renewal with barrier maintenance to withstand environmental stress and shield against pathogens. Here, we identify a microbial-immune-epithelial feedback mechanism that integrates environmental information into stem cell regulation. Specifically, we show that Langerhans cells--an intra-epithelial macrophage population-- orchestrate this circuit by producing prostaglandin E2, which restrains stem cell proliferation, promotes epidermal differentiation and maintains barrier integrity during homeostasis. Upon pathway disruption, stem cells become overactivated, impairing differentiation and compromising barrier function. Upstream, Langerhans cell activity is tuned by the local microbial environment in a rheostat-like fashion, coupling commensal sensing to stem cell control. Our findings provide a general framework for how barrier tissues achieve adaptive homeostasis amid continual external challenge.

immunology↗

bioRxiv2022

A lymphatic-stem cell interactome regulates intestinal stem cell activity

Barrier epithelia depend on resident stem cells for homeostasis, defense and repair. Intestinal stem cells (ISCs) of the small and large intestines respond to their local microenvironments (niches) to fulfill a continuous demand for tissue turnover, yet the complexity of their niches is still unfolding. Here, we report an extensive lymphatic network that intimately associates with ISCs within these niches. Devising a lymphatic:organoid coculture system, we show that lymphatic-secreted factors maintain ISCs while inhibiting precocious differentiation. Employing a new deconvolution algorithm, BayesPrism, to pair single-cell and spatial transcriptomics, we cartograph the lymphatic ligand:ISC receptor interactomes at high resolution. We unearth crypt lymphatics as a major source of WNT-signaling factors (WNT2, R-SPONDIN-3) known to drive ISC behavior, and REELIN, a hitherto unappreciated ISC regulator secreted by crypt lymphatics. Together, our studies expose lymphatics as a central hub for niche factors that govern the regenerative potential of ISCs.

cell biology↗

bioRxiv2021

Vγ usage distinguishes pro- and anti-tumor intestinal γδ T cell subsets

{gamma}{delta} T cells physiologically scan the intestinal epithelium, representing a substantial fraction of infiltrating lymphocytes in colorectal cancer (CRC), albeit their role in CRC remains unclear. Using murine CRC models, we found that most {gamma}{delta} T cells in pre- or non-tumor colon express V{gamma}1+ or V{gamma}7+ and exhibit a cytotoxic profile. Targeting these {gamma}{delta} T cell subsets, as well as conditionally interfering with {gamma}{delta} T cell function at early stages of tumorigenesis led to heightened tumor development, suggesting anti-CRC functions for V{gamma}1+ and V{gamma}7+ subsets. In contrast, ROR{gamma}t+ {gamma}{delta} T cell subsets, including V{gamma}4+ and microbiotadependent V{gamma}6+, accumulated during CRC progression. Conditional deletion of ROR{gamma}t or V{gamma} chains revealed redundant roles for IL-17-producing V{gamma}4+ and V{gamma}6+ {gamma}{delta} T cells in promoting tumor growth. Our results uncover pro- and anti-tumor roles for {gamma}{delta} T cell subsets.

immunology↗