Biology subjects

Strobl, J.

Publications and source records attributed to Strobl, J..

5 recordsLinked to original sources

bioRxiv2026

Tissue-resident memory T cells are diminished in the Kaposi sarcoma tumor microenvironment of people living with HIV

Kaposi sarcoma (KS) is a rare neoplasm and an AIDS-defining diagnosis in people living with HIV (PLWH). Although and chronic infection with Kaposi sarcoma-associated herpesvirus (KSHV) contributes to KS progression, the local immune mechanisms that are lost during tumor progression remain incompletely understood. Here, we systematically characterized global patterns in the KS tumor microenvironment (TME) in both PLWH and HIV-negative individuals. Spatial transcriptomics revealed distinct niches comprising of tumor cells, immune cells, and surrounding skin cells. Tumor regions expressed a characteristic endothelial-fibroblastic signature attributable to KS tumor cells (CD34, LYVE1, SCN9A), TME regions expressed marker genes for T cells, B cells and cancer-associated fibroblasts. Analysis of putative cell-cell interactions demonstrated that tumor cells preferentially interact with cells of the TME, including T cells, indicating an important role as hub of cellular communication in KS. Immunofluorescence imaging confirmed increased numbers of T cells, specifically tissue-resident memory T cells (TRM), in KS samples compared to healthy skin, accompanied by a pronounced upregulation of PD-1 expression that was predominantly localized to the TME. Notably, we identified HIV-associated alterations in the KS immune microenvironment: PLWH exhibited loss of CXCR3+ and IFN-gamma producing CD8+ TRM cells in the KS TME compared to HIV-negative patients, a finding consistent with impaired antitumor immunity. Together, our findings reveal HIV-associated disruption of functional anti-tumor immunity in the KS TME of PLWH. Increased PD-1 expression within T cells of the TME highlights potential therapeutic use of immune checkpoint inhibitors in KS.

immunology↗

bioRxiv2026

A scRNA-seq atlas of chronic inflammatory skin diseases

Inflammatory skin diseases (ISDs) affect up to 25% of the global population. Yet, large-scale comparative single-cell RNA-sequencing (scRNA-seq) analyses between ISDs are still missing. Here, we integrated scRNA-seq datasets spanning 27 skin diseases from 50 studies, comprising over 2 million cells from 441 samples. Using the healthy skin cell atlas as reference, we could build a robust ISD atlas that enabled us to differentiate universal inflammatory signatures and disease-specific ones. This highlighted, for example, a shared gene program between keratinocytes in atopic dermatitis and parapsoriasis, not present in cutaneous T-cell lymphoma, confirms the plasticity of Th17 cells throughout ISDs, defines specific macrophage signatures in acne, and reveals a yet undescribed role of mural cells in ISDs. This demonstrates the power of the ISD atlas as a resource to resolve disease-specific immune mechanisms. The complete atlas is available through an interactive online portal at https://isd-atlas.derma.meduniwien.ac.at.

immunology↗

bioRxiv2024

Unveiling Stimulus Transduction Artifacts in Auditory Steady-State Response Experiments: Characterization, Risks, and Mitigation Strategies

This scientific paper addresses the potential risk of spurious responses in neuroscientific auditory steady-state response (ASSR) experiments attributed to transduction artifacts. The focus is particularly on click train stimuli, given their spectral content in the frequency range of interest (e.g., 40 Hz). Building upon a pilot experiment demonstrating the existence of the artifact in a phantom head, this study focuses on the characterization of stimulus artifacts in extended measurements with phantoms and the evaluation of associated risks in experiments involving human subjects. The investigation is divided into two parts: the first part scrutinizes stimulus artifact properties crucial for mitigation, while the second part assesses risks in ASSR experiments with human subjects based on the characterized artifact. The discussion covers stimulus characterization, experimental setups with phantoms, and experiments with human subjects, exploring potential sources of the artifact, its spatial properties, and the influence of re-referencing. The results reveal the role of headphone cables as a source of stimulus artifacts, along with the surprising impact of headphone transducers. The study emphasizes the need for careful experimental design and data analysis to avoid misinterpretations of stimulus artifacts as genuine brain responses in ASSR experiments.

neuroscience↗

bioRxiv2023

Cutaneous T cell lymphoma atlas reveals malignant Th2 cells supported by a B cell-rich microenvironment

Cutaneous T-cell lymphoma (CTCL) is a potentially fatal clonal malignancy of T cells primarily affecting the skin. The most common form of CTCL, mycosis fungoides (MF), can be difficult to diagnose resulting in treatment delay. The pathogenesis of CTCL is not fully understood due to limited data from patient studies. We performed single-cell RNA sequencing and spatial transcriptomics profiling of skin from patients with MF-type CTCL, and an integrated comparative analysis with human skin cell atlas datasets from healthy skin, atopic dermatitis and psoriasis. We reveal the co-optation of Th2-immune gene programmes by malignant CTCL cells and modelling of the tumour microenvironment to support their survival. We identify MHC-II+ fibroblast subsets reminiscent of lymph node T-zone reticular cells and monocyte-derived dendritic cells that can maintain Th2-like tumour cells. CTCL Th2-like tumour cells are spatially associated with B cells, forming aggregates reminiscent of tertiary lymphoid structures which are more prominent with progressive disease. Finally, we validated the enrichment of B cells in CTCL skin infiltrates and its association with disease progression across three independent patient cohorts. Our findings provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for CTCL.

genomics↗

bioRxiv2023

Scarring hair follicle destruction is driven by the collapse of EGFR-protected JAK-STAT1-sensitive stem cell immune privilege

The hair follicle stem cell niche is an immune-privileged microenvironment, characterised by suppressed antigen presentation, thus shielding against permanent immune-mediated tissue damage. In this study, we demonstrate the protective role of hair follicle-specific epidermal growth factor receptor (EGFR) from scarring hair follicle degeneration. Mechanistically, disruption of EGFR signalling generates a cell intrinsic hypersensitivity within the JAK-STAT1 pathway, compromising the immune privilege in the context of CD8 T cell and NK cell-mediated inflammation. Genetic depletion of either JAK1/2 or STAT1 or topical therapeutic inhibition of JAK1/2 restores the immune privilege and activates stem cells to resume hair growth in mouse models of epidermal and hair follicle specific EGFR deletion. Skin biopsies from EGFR inhibitor-treated and from EGFR-independent cicatricial alopecia patients indicate active STAT1 signalling within the hair follicles. Notably, a case study of folliculitis decalvans, characterised by progressive hair loss, scaling and perifollicular erythema, demonstrates successful treatment with systemic JAK1/2 inhibition. Our findings offer mechanistic insights and present a therapeutic strategy for addressing scarring hair follicle destruction associated with EGFR-inhibitor therapy and cicatricial alopecia.

immunology↗