TSLP acts on infiltrating effector T cells to drive allergic skin inflammation
TSLP acts on infiltrating effector T cells to drive allergic skin inflammation
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DOI：
10.1073/pnas.0801532105
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发表时间：
2008-08-19
影响因子：
11.1
通讯作者：
Geha, Raif S.
中科院分区：
文献类型：
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作者：
He, Rui;Oyoshi, Michiko K.;Geha, Raif S.
胸腺基质淋巴生成素（TSLP）是一种由上皮细胞（包括角质形成细胞）表达的细胞因子，在过敏性炎症中起重要作用。卵清蛋白（OVA）是一种潜在的特应性皮炎模型，经小鼠表皮免疫引起的过敏性皮肤炎症在TSLPR-/-小鼠中严重受损，表现为嗜酸性粒细胞浸润减少，局部T辅助2 （Th2）细胞因子表达减少。然而，表皮致敏的TSLPR-/-小鼠的脾细胞分泌Th2细胞因子对OVA的反应是正常的。TSLPR-/-小鼠的皮肤树突状细胞迁移到引流淋巴结、表达激活标记物、诱导增殖和Th2细胞因子由幼稚T细胞产生的能力正常。TSLPR-/-小鼠的CD4(+) T细胞正常表达皮肤归巢受体e -选择素配体，并正常归巢到皮肤，但不能将过敏性皮肤炎症转移给WT受体。TSLP通过靶向TSLPR作用于抗原特异性T细胞，促进体外Th2细胞因子的分泌。皮下注射抗tslp可阻断OVA免疫WT小鼠皮肤抗原刺激后过敏性皮肤炎症的发生。这些发现表明，TSLP是抗原驱动的Th2细胞因子通过皮肤浸润效应T细胞分泌所必需的，可能是过敏性皮肤炎症的治疗靶点。
Thymic stromal lymphopoietin (TSLP) is a cytokine expressed by epithelial cells, including keratinocytes, and is important in allergic inflammation. Allergic skin inflammation elicited by epicutaneous immunization of mice with ovalbumin (OVA), a potential model of atopic dermatitis, was severely impaired in TSLPR-/- mice, as evidenced by decreased infiltration of eosinophils and decreased local expression of T helper 2 (Th2) cytokines. However, secretion of Th2 cytokines by splenocytes from epicutaneous sensitized TSLPR-/- mice in response to OVA was normal. Skin dendritic cells from TSLPR-/- mice were normal in their ability to migrate to draining lymph nodes, express activation markers, and induce proliferation and Th2 cytokine production by naive T cells. CD4(+) T cells from TSLPR-/- mice expressed the skin homing receptor E-selectin ligand normally, and homed to the skin normally, but failed to transfer allergic skin inflammation to WT recipients. TSLP enhanced Th2 cytokine secretion in vitro by targeting TSLPR on antigen specific T cells. Intradermal injection of anti-TSLP blocked the development of allergic skin inflammation after cutaneous antigen challenge of OVA immunized WT mice. These findings suggest that TSLP is essential for antigen driven Th2 cytokine secretion by skin infiltrating effector T cells and could be a therapeutic target in allergic skin inflammation.