Tuzova Marina, Richmond Jillian, Wolpowitz Deon, Curiel-Lewandrowski Clara, Chaney Keri, Kupper Thomas, Cruikshank William
Pulmonary Center.
Leuk Lymphoma. 2015 Feb;56(2):440-9. doi: 10.3109/10428194.2014.919634. Epub 2014 Jun 6.
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.
蕈样肉芽肿（MF）的特征是CCR4⁺CCR7⁻效应记忆T细胞在皮肤中积聚；然而，其招募机制尚未明确。胸腺基质淋巴细胞生成素（TSLP）是一种由角质形成细胞衍生的细胞因子，可触发Th2免疫反应，并与特应性皮炎中T细胞向皮肤的募集有关。白细胞介素-16（IL-16）是CD4⁺T细胞的趋化因子和生长因子。我们推测TSLP和IL-16可能有助于MF中恶性T细胞的募集。我们发现，在CCL22升高之前，极早期患者的血浆和皮肤活检组织中TSLP和IL-16就已升高。TSLP和IL-16均可诱导CCR4⁺TSLPR⁺CD4⁺CCR7⁻CD31⁺细胞的迁移反应，这是皮肤中恶性T细胞的特征。共刺激也导致显著的增殖反应。我们得出结论，在疾病早期表达的TSLP和IL-16具有将恶性T细胞招募到皮肤并促进其增殖增强的作用。
