Biology subjects

Jameson, J.

Publications and source records attributed to Jameson, J..

5 recordsLinked to original sources

bioRxiv2025

TNFR2 is Expressed by a Discrete Subset of Epidermal γ δ T Cells with an IL-17 Gene Signature during Psoriasis

Psoriasis is a chronic skin disease that results in scaly patches and affects 2-3% of people worldwide. Therapeutic treatment targets the TNF-/IL-17 axis to disrupt keratinocyte hyperproliferation and inflammation. While more is known about the role of dermal {beta} and {gamma}{delta} T cells in IL-17 production, less is understood about the role of resident epidermal T cells. Here, we examine how TNF- modulates epidermal {gamma}{delta} T cell activation and function. We show that a subset of activated epidermal {gamma}{delta} T cells expresses TNFR2 with or without TNFR1. Stimulation with TNF- induces epidermal {gamma}{delta} T cells to produce IL-17 family cytokines and chemokines. Epidermal {gamma}{delta} T cells do not require TNFR1 or 2 for development or homing to the skin. Instead, TNFR2 plays roles in epidermal {gamma}{delta} T cell function skewing them toward a T{gamma}{delta}17 phenotype during psoriasis. Investigation of the mechanisms by which TNF- associated inflammation impacts epidermal {gamma}{delta} T cell function may help identify new cellular targets for immunotherapy or mark them as early regulators of skin inflammation.

immunology↗

bioRxiv2025

Epidermal γδ T cells, CD8 T cells and macrophages are increased in number in alopecia areata and express BST2 as part of an interferon-driven antiviral gene signature

Alopecia areata is an autoimmune disorder affecting approximately 2% of the global population, characterized by immune-mediated disruption of hair follicle immune privilege and unpredictable hair loss. While CD4 and CD8 T cells are established drivers of pathogenesis, the roles of other immune cell populations remain incompletely defined. Here, we reaffirm the pathogenic role of CD8 T cells and identify a contribution of epidermal {gamma}{delta} T cells and macrophages to alopecia areata. Using publicly available single-cell RNA sequencing (scRNAseq) data from the skin of C3H/HeJ mice with alopecia areata, we demonstrate that epidermal {gamma}{delta} T cells upregulate genes associated with immune homeostasis, proliferation, and inflammation, including BST2, an interferon-stimulated antiviral protein. In vivo, epidermal {gamma}{delta} T cells and keratinocytes are increased in number, with BST2 expression enriched around hair follicles. BST2 is also expressed on CD8 T cells actively producing IFN-{gamma} and on CD11b+ macrophages with signatures of antiviral and complement system pathways. In human alopecia areata skin, BST2 expression is elevated in alopecia areata and downregulated following treatment with the JAK inhibitor tofacitinib. Together, these findings position BST2 as a marker of interferon-driven immune activation and highlight epidermal {gamma}{delta} T cells as a contributor to alopecia areata pathogenesis.

immunology↗

bioRxiv2025

Skin Resident T Cell Interactions with NPY1R+ Neurons During Wound Repair Are Impaired by Obesity

Wound repair involves complex cellular interactions to induce efficient healing. Skin resident {gamma}{delta} T cells regulate keratinocyte function and inflammatory responses in wound healing through the secretion of growth factors and cytokines. Some of these cytokines are involved in the neuroimmune axis, so we aimed to ascertain if {gamma}{delta} T cells and neurons exhibit crosstalk during wound repair. We identified a prevalent NPY1R+ peripheral neuron subset in the skin. {gamma}{delta} T cells interact with NPY1R+ neurons in the epidermis and dermis of both nonwounded and wounded murine skin. To determine the impact of the {gamma}{delta} TCR on NPY1R+ neuron interactions in wound healing, we compared epidermal T cell-neuron interactions in TCR{delta}-/- mice during wound repair. We found a decrease in interactions between epidermal {beta} T cells and NPY1R+ neurons in TCR{delta}-/- mice, suggesting {gamma}{delta} T cells communicate with NPY1R+ neurons more frequently than {beta} T cells in the epidermis, regardless of wound repair. In contrast, dermal T cell-neuron interactions in wildtype and TCR{delta}-/- mice during wound repair were similar between {beta} T cells and {gamma}{delta} T cells, suggesting both T cell types mediate communications with neurons in the dermis. In obese mice there are fewer NPY1R+ neurons and diminished neuron-T cell interactions indicative of neuropathy. Together these findings elucidate a neuroimmune crosstalk during wound repair that becomes disrupted in obesity.

immunology↗

bioRxiv2024

Impact of Obesity on the CCR6-CCL20 Axis in Epidermal γδ T Cells and IL-17A Production in Murine Wound Healing and Psoriasis

Obesity is associated with comorbidities including type 2 diabetes, chronic nonhealing wounds and psoriasis. Normally skin homeostasis and repair is regulated through the production of cytokines and growth factors derived from skin-resident cells including epidermal {gamma}{delta} T cells. However epidermal {gamma}{delta} T cells exhibit reduced proliferation and defective growth factor and cytokine production during obesity and type 2 diabetes. One of the genes modulated in epidermal {gamma}{delta} T cells during obesity and type 2 diabetes is CCR6, which is the receptor for CCL20. CCL20 is elevated in the skin during obesity and type 2 diabetes. Here we identify a subset of murine epidermal {gamma}{delta} T cells that expresses CCR6 in response to activation in vitro and post-wounding or psoriasis induction with imiquimod in vivo. We show that CCL20 stimulates epidermal {gamma}{delta} T cells to produce IL-17 suggesting CCR6 regulates the IL-17 axis as in dermal {gamma}{delta} T cells. Further, epidermal {gamma}{delta} T cells upregulate CCR6 and produce IL-17 during murine models of wound repair and psoriasis. Obesity increases CCR6 and IL-17 expression by epidermal {gamma}{delta} T cells during wound repair but has less of an effect during psoriasis. These findings have novel implications for the regulation of a specific population of IL-17-producing epidermal {gamma}{delta} T cells during skin damage and inflammation.

immunology↗

bioRxiv2023

Tick extracellular vesicles impair epidermal homeostasis through immune-epithelial networks during hematophagy

Wound healing has been extensively studied through the lens of inflammatory disorders and cancer, but limited attention has been given to hematophagy and arthropod-borne diseases. Hematophagous ectoparasites, including ticks, subvert the wound healing response to maintain prolonged attachment and facilitate blood-feeding. Here, we unveil a strategy by which extracellular vesicles (EVs) ensure blood-feeding and arthropod survival in three medically relevant tick species. Through single cell RNA sequencing and murine genetics, we demonstrate that wildtype animals infested with EV-deficient Ixodes scapularis display a unique epidermal sub-population with a mesenchymal-like transcriptional program and an overrepresentation of pathways connected to wound healing. Furthermore, tick EVs inhibit proliferation and diminish the capacity of wound closure in keratinocytes. This occurrence was linked to phosphoinositide 3-kinase activity, keratinocyte growth factor 1 (KGF-1) and transforming growth factor {beta} (TGF-{beta}) levels. Collectively, we uncovered a strategy employed by a blood-feeding arthropod that disrupts the circuitry in cutaneous wound healing, contributing to ectoparasite fitness.

microbiology↗