Ferroptosis of select skin epithelial cells initiates and maintains chronic systemic immune-mediated psoriatic disease.

Dysregulations of epithelial-immune interactions frequently culminate in chronic inflammatory diseases of the skin, lungs, kidneys, and gastrointestinal tract. Yet, the intraepithelial processes that initiate and perpetuate inflammation in these organs are poorly understood. Here, by utilizing redox lipidomics we identified ferroptosis-associated peroxidation of polyunsaturated phosphatidylethanolamines in the epithelia of patients with asthma, cystic fibrosis, psoriasis, and renal failure.

Unleashed monocytic engagement in Sézary syndrome during the combination of anti-CCR4 antibody with type I interferon.

Sézary syndrome (SS) is an aggressive leukemic expansion of skin-derived malignant CD4+ T cells. Drug monotherapy often results in disease relapse because of the heterogenous nature of malignant CD4+ T cells, but how therapies can be optimally combined remains unclear because of limitations in understanding the disease pathogenesis. We identified immunologic transitions that interlink mycosis fungoides with SS using single-cell transcriptome analysis in parallel with high-throughput T-cell receptor sequencing.

Deciphering Tumor Cell Evolution in Cutaneous T-Cell Lymphomas: Distinct Differentiation Trajectories in Mycosis Fungoides and Sézary Syndrome.

Cutaneous T-cell lymphomas are a heterogeneous group of neoplasms originating in the skin, with mycosis fungoides (MF) and Sézary syndrome (SS) representing the most common variants. The cellular origin of cutaneous lymphomas has remained controversial owing to their immense phenotypic heterogeneity that obfuscates lineage reconstruction on the basis of classical surface biomarkers. To overcome this heterogeneity and reconstruct the differentiation trajectory of malignant cells in MF and SS, TCR sequencing was performed in parallel with targeted transcriptomics at the single-cell resolution among cutaneous samples in MF and SS.

Melanoma-associated repair-like Schwann cells suppress anti-tumor T-cells via 12/15-LOX/COX2-associated eicosanoid production.

Peripheral glia, specifically the Schwann cells (SCs), have been implicated in the formation of the tumor microenvironment (TME) and in cancer progression. However, and analyses of how cancers reprogram SC functions in different organs of tumor-bearing mice are lacking. We generated Plp1-CreERT/tdTomato mice which harbor fluorescently labeled myelinated and non-myelin forming SCs.

Tumor-Induced T Cell Polarization by Schwann Cells.

Nerve-cancer crosstalk resulting in either tumor neurogenesis or intratumoral neurodegeneration is critically controlled by Schwann cells, the principal glial cells of the peripheral nervous system. Though the direct stimulating effect of Schwann cells on malignant cell proliferation, motility, epithelial-mesenchymal transition, and the formation of metastases have been intensively investigated, the ability of Schwann cells to affect the effector and regulatory immune cells in the tumor environment is significantly less studied. Here, we demonstrated that tumor cells could stimulate Schwann cells to produce high levels of prostaglandin E, which could be blocked by COX-2 inhibitors.