Intradermal administration of thymic stromal lymphopoietin induces a T cell- and eosinophil-dependent systemic Th2 inflammatory response
Intradermal administration of thymic stromal lymphopoietin induces a T cell- and eosinophil-dependent systemic Th2 inflammatory response
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DOI：
10.4049/jimmunol.181.6.4311
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发表时间：
2008-09-15
影响因子：
4.4
通讯作者：
Comeau, Michael R.
中科院分区：
文献类型：
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作者：
Jessup, Heidi K.;Brewer, Avery W.;Comeau, Michael R.
上皮来源的细胞因子胸腺基质淋巴生成素（TSLP）在转基因小鼠中选择性过表达，或局部应用维生素D3或低钙类似物驱动时，足以诱导哮喘或特应性皮炎样表型。尽管在这些模型中，T细胞和B细胞在TSLP诱导的炎症中是不可缺少的，但对TSLP驱动的炎症反应的下游途径或其他细胞类型知之甚少。为了表征TSLP在体内的下游作用，我们研究了外源给药TSLP蛋白对野生型和遗传缺陷小鼠的影响。TSLP诱导了系统性Th2炎症反应，其特征是循环IgE和IgG1增加，引流淋巴结大小和细胞数量增加，引流淋巴结培养物中Th2细胞因子产生增加，炎症细胞浸润，上皮增生，皮下纤维化，皮肤中Th2细胞因子和趋化因子信息上调。在各种基因缺陷小鼠中对TSLP的反应表明，T细胞和嗜酸性粒细胞是必需的，而肥大细胞和tnf - α是可缺性的。在IL-41和il -13缺乏的小鼠中，tslp诱导的反应显著但不完全减少。这些结果揭示了参与tslp诱导炎症的途径和细胞类型。
The epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) is sufficient to induce asthma or atopic dermatitis-like phenotypes when selectively overexpressed in transgenic mice, or when driven by topical application of vitamin D3 or low-calcemic analogues. Although T and B cells have been reported to be dispensable for the TSLP-induced inflammation in these models, little is known about the downstream pathways or additional cell types involved in the inflammatory response driven by TSLP. To characterize the downstream effects of TSLP in vivo, we examined the effects of exogenous administration of TSLP protein to wild-type and genetically deficient mice. TSLP induced a systemic Th2 inflammatory response characterized by increased circulating IgE and IgG1 as well as increased draining lymph node size and cellularity, Th2 cytokine production in draining lymph node cultures, inflammatory cell infiltrates, epithelial hyperplasia, subcuticular fibrosis, and up-regulated Th2 cytokine and chemokine messages in the skin. Responses to TSLP in various genetically deficient mice demonstrated T cells and eosinophils were required, whereas mast cells and TNF-alpha were dispensable. TSLP-induced responses were significantly, but not completely reduced in IL-41 and IL-13-deficient mice. These results shed light on the pathways and cell types involved in TSLP-induced inflammation.