Abstract
Mycosis fungoides (MF) is characterized by skin accumulation of CCR4+CCR7- effector memory T cells; however the mechanism for their recruitment is not clearly identified. Thymic Stromal Lymphopoietin (TSLP) is a keratinocyte-derived cytokine that triggers Th2 immunity and is associated with T cell recruitment to the skin in atopic dermatitis. Interleukin-16 (IL-16) is a chemoattractant and growth factor for CD4+T cells. We hypothesized that TSLP and IL-16 could contribute to recruitment of malignant T cells in MF. We found elevated TSLP and IL-16 in very early stage patients' plasma and skin biopsies, prior to elevation in CCL22. Both TSLP and IL-16 induced migratory responses of CCR4+TSLPR+CD4+CCR7-CD31+cells, characteristic of malignant T cells in the skin. Co-stimulation also resulted in significant proliferative responses. We conclude that TSLP and IL-16, expressed at early stages of disease, function to recruit malignant T cells to the skin and contribute to their enhanced proliferation.
Keywords:
Thymic stromal lymphopoietin (TSLP); cutaneous T cell lymphoma (CTCL); interleukin-16 (IL-16); mycosis fungoides (MF).
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adult
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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Cell Movement / drug effects
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Cell Movement / immunology
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Cell Proliferation / drug effects
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Cells, Cultured
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Chemokine CCL22 / immunology
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Chemokine CCL22 / metabolism
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Cytokines / immunology*
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Cytokines / metabolism
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Cytokines / pharmacology
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Female
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Flow Cytometry
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Humans
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Interleukin-16 / immunology*
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Interleukin-16 / metabolism
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Interleukin-16 / pharmacology
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Male
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Microscopy, Fluorescence
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Middle Aged
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Mycosis Fungoides / blood
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Mycosis Fungoides / immunology*
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Mycosis Fungoides / metabolism
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Platelet Endothelial Cell Adhesion Molecule-1 / immunology
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Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
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Receptors, CCR4 / immunology*
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Receptors, CCR4 / metabolism
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Receptors, Cytokine / immunology
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Receptors, Cytokine / metabolism
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Skin / immunology
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Skin / metabolism
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Skin / pathology
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Skin Neoplasms / blood
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Skin Neoplasms / immunology*
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Skin Neoplasms / metabolism
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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Thymic Stromal Lymphopoietin
Substances
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CCR4 protein, human
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CRLF2 protein, human
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Chemokine CCL22
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Cytokines
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Interleukin-16
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Platelet Endothelial Cell Adhesion Molecule-1
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Receptors, CCR4
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Receptors, Cytokine
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Thymic Stromal Lymphopoietin