Hair follicle-derived IL-7 and IL-15 mediate skin-resident memory T cell homeostasis and lymphoma.
Hair follicle-derived IL-7 and IL-15 mediate skin-resident memory T cell homeostasis and lymphoma.
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DOI：
10.1038/nm.3962
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发表时间：
2015-11
期刊：
影响因子：
82.9
通讯作者：
Nagao K
中科院分区：
文献类型：
--
作者：
Adachi T;Kobayashi T;Sugihara E;Yamada T;Ikuta K;Pittaluga S;Saya H;Amagai M;Nagao K
皮肤含有多种常驻白细胞亚群，必须对其进行严格调控以维持免疫稳态。毛囊是皮肤中独特的结构，通过产生趋化因子有助于皮肤树突状细胞的稳态。我们证明，负责长期皮肤免疫的CD4 +和CD8 +皮肤驻留记忆T细胞（TRM）主要位于未受扰动的表皮的毛囊上皮内。TRM对表皮和毛囊的趋向性在此被称为向表皮性。毛囊衍生的IL - 15是CD8 + TRM所必需的，IL - 7是CD8 +和CD4 + TRM所必需的，以发挥向表皮性。缺乏任何一种细胞因子都会损害半抗原诱导的接触性超敏反应。在皮肤T细胞淋巴瘤模型中，向表皮性CD4 + TRM淋巴瘤细胞的定位取决于毛囊衍生的IL - 7。这些发现表明毛囊衍生的细胞因子是恶性和非恶性TRM细胞组织驻留的调节因子，并提示它们可能成为炎症性皮肤病和淋巴瘤的治疗靶点。
The skin harbors a variety of resident leukocyte subsets that must be tightly regulated to maintain immune homeostasis. Hair follicles are unique structures in the skin that contribute to skin dendritic cell homeostasis via chemokine production. We demonstrate that CD4+ and CD8+ skin resident memory T cells (TRM), responsible for long-term skin immunity, resided predominantly within the hair follicle epithelium of unperturbed epidermis. TRM tropism for the epidermis and follicles was herein termed epidermotropism. Hair follicle-derived IL-15 was required for CD8+ TRM, and IL-7 for CD8+ and CD4+ TRM, to exert epidermotropism. The lack of either cytokine impaired hapten-induced contact hypersensitivity responses. In a model of cutaneous T cell lymphoma, epidermotropic CD4+ TRM lymphoma cell localization depended on hair follicle-derived IL-7. These findings implicate hair follicle-derived cytokines as regulators of malignant and non-malignant TRM cell tissue residence and suggest they may be targeted therapeutically in inflammatory skin disease and lymphoma.