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.

Keywords::

• Thymic stromal lymphopoietin (TSLP)
• interleukin-16 (IL-16)
• mycosis fungoides (MF)
• cutaneous T cell lymphoma (CTCL)

Acknowledgements

The authors thank Natalie Adams and Lynne Morrison, who consented patients with MF and collected blood samples at Dana Farber Cancer Institute and Arizona Cancer Center. We also thank Oksana Hradyska and Phillip Vartanyan for technical assistance.

All flow cytometric data were acquired using equipment maintained by the Boston University Medical Campus Flow Cytometry Core Facilities.

This work was supported by NIH grant 1R01CA122737.

Potential conflict of interest:

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