title: CCR4+T cell recruitment to the skin in mycosis fungoides: potential contributions by thymic stromal lymphopoietin and interleukin-16.
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.
authors.affiliation: Pulmonary Center.
authors.forename: Marina
authors.initials: M
authors.lastname: Tuzova
authors.forename: Jillian
authors.initials: J
authors.lastname: Richmond
authors.forename: Deon
authors.initials: D
authors.lastname: Wolpowitz
authors.forename: Clara
authors.initials: C
authors.lastname: Curiel-Lewandrowski
authors.forename: Keri
authors.initials: K
authors.lastname: Chaney
authors.forename: Thomas
authors.initials: T
authors.lastname: Kupper
authors.forename: William
authors.initials: W
authors.lastname: Cruikshank
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054422:Chemokine CCL22 / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019410:Interleukin-16 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D054398:Receptors, CCR4 / Q000276:immunology* / Q000378:metabolism; D018121:Receptors, Cytokine / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
chemical_list: C515354:CCR4 protein, human; C498762:CRLF2 protein, human; D054422:Chemokine CCL22; D016207:Cytokines; D019410:Interleukin-16; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D054398:Receptors, CCR4; D018121:Receptors, Cytokine; D000094632:Thymic Stromal Lymphopoietin
keywords: Thymic stromal lymphopoietin (TSLP); cutaneous T cell lymphoma (CTCL); interleukin-16 (IL-16); mycosis fungoides (MF)