TSLP promotes induction of Th2 differentiation but is not necessary during established allergen-induced pulmonary disease.
TSLP promotes induction of Th2 differentiation but is not necessary during established allergen-induced pulmonary disease.
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DOI：
10.1371/journal.pone.0056433
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lukacs NW
中科院分区：
文献类型：
--
作者：
Jang S;Morris S;Lukacs NW
胸腺基质淋巴细胞生成素 (TSLP) 通过促进 Th2 型反应参与过敏性炎症的发生，并已成为潜在的治疗靶点。使用体外 T 细胞分化培养物，我们能够验证 TSLP 在 Th2 免疫反应的早期发展中发挥着更关键的作用，而对已发展的 Th2 反应的增强作用不太显着。过继转移幼稚 DO11.10 卵清蛋白特异性 T 细胞，然后气道暴露于卵清蛋白，结果表明，与野生型小鼠相比，TSLP−/− 小鼠在 Th2 反应发展过程中 Th2 免疫反应早期受损。相反，与转移到野生型小鼠中相比，将已分化的 Th2 细胞转移到 TSLP−/− 小鼠中并不会改变卵清蛋白攻击后的肺病理学或 Th2 细胞因子的产生。过敏原诱导的 Th2 气道模型表明，野生型和 TSLP−/− 小鼠之间仅 gob5（粘液相关基因）表达存在差异。此外，当患有既定疾病的过敏动物用中和性抗 TSLP 抗体治疗时，与对照抗体治疗的动物相比，气道高反应性 (AHR) 或 Th2 细胞因子的产生没有变化，而与 TSLP−/− 小鼠研究类似，也观察到了 gob5 基因表达的变化。相比之下，当动物在过敏原致敏的初始阶段接受抗 TSLP 治疗时，在最后的过敏原激发过程中 Th2 细胞因子发生显着变化。总的来说，这些研究表明，在小鼠中，TSLP 在 Th2 免疫反应的早期发展过程中发挥着重要作用，而其在过敏性疾病后期的作用对于维持 Th2 驱动的过敏性疾病可能并不那么重要。
Thymic stromal lymphopoietin (TSLP) has been implicated in the development of allergic inflammation by promoting Th2-type responses and has become a potential therapeutic target. Using in vitro T cell differentiation cultures we were able to validate that TSLP played a more critical role in the early development of Th2 immune responses with less significant enhancement of already developed Th2 responses. Adoptive transfer of naive DO11.10 ovalbumin-specific T cells followed by airway exposure to ovalbumin showed an early impairment of Th2 immune response in TSLP−/− mice compared to wild type mice during the development of a Th2 response. In contrast, transfer of already differentiated Th2 cells into TSLP−/− mice did not change lung pathology or Th2 cytokine production upon ovalbumin challenge compared to transfer into wild type mice. An allergen-induced Th2 airway model demonstrated that there was only a difference in gob5 expression (a mucus-associated gene) between wild type and TSLP−/− mice. Furthermore, when allergic animals with established disease were treated with a neutralizing anti-TSLP antibody there was no change in airway hyperreponsiveness (AHR) or Th2 cytokine production compared to the control antibody treated animals, whereas a change in gob5 gene expression was also observed similar to the TSLP−/− mouse studies. In contrast, when animals were treated with anti-TSLP during the initial stages of allergen sensitization there was a significant change in Th2 cytokines during the final allergen challenge. Collectively, these studies suggest that in mice TSLP has an important role during the early development of Th2 immune responses, whereas its role at later stages of allergic disease may not be as critical for maintaining the Th2-driven allergic disease.
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影响因子：
14.2
作者：
Lee, Hai-Chon;Headley, Mark B.;Loo, Yueh-Ming;Berlin, Aaron;Gale, Michael, Jr.;Debley, Jason S.;Lukacs, Nicholas W.;Ziegler, Steven F.
通讯作者：
Ziegler, Steven F.
TSLP和IL-7使用两种不同的机制来调节人CD4+ T细胞稳态。
影响因子：
15.3
作者：
Lu, Ning;Wang, Yi-Hong;Wang, Yui-Hsi;Arima, Kazuhiko;Hanabuchi, Shino;Liu, Yong-Jun
通讯作者：
Liu, Yong-Jun
DOI：
10.4049/jimmunol.0902447
发表时间：
2010-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kim S;Prout M;Ramshaw H;Lopez AF;LeGros G;Min B
通讯作者：
Min B
影响因子：
20.3
作者：
Mazzucchelli, Renata;Hixon, Julie A.;Durum, Scott K.
通讯作者：
Durum, Scott K.
影响因子：
6.5
作者：
Iwasaki, M;Nagata, K;Ikezawa, Z
通讯作者：
Ikezawa, Z