Thymic stromal lymphopoietin (TSLP) is a critical upstream cytokine inducing type 2 inflammation in various diseases, including asthma and atopic dermatitis. Accumulating evidence suggests that TSLP can directly stimulate a variety of immune cells, such as dendritic cells (DCs), basophils, T cells, and group 2 innate lymphoid cells (ILC2s). However, which cell types directly respond to TSLP in vivo and how TSLP initiates type 2 inflammation has remained controversial. To define the precise role of TSLP in vivo, for the first time we generated multiple cell lineage-specific TSLP receptor-deficient mice to systematically dissect the cell-intrinsic requirements for TSLP responsiveness in type 2 inflammation in the lung. In papain-induced innate immune-mediated type 2 airway inflammation, TSLP directly stimulated ILC2s, but not basophils, leading to enhanced type 2 inflammation. On the other hand, in OVA-induced adaptive immune-mediated type 2 airway inflammation, TSLP principally acted on DCs and CD4 + T cells during the sensitization phase, but not basophils or ILC2s, and facilitated the development of Th2 cell-mediated airway inflammation. Together, these findings reveal that TSLP activates distinct immune cell cascades in the context of innate and adaptive immune-mediated type 2 inflammation.

中文翻译：

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靶向删除 TSLP 受体揭示了促进 2 型气道炎症的细胞机制。

胸腺基质淋巴细胞生成素 (TSLP) 是一种关键的上游细胞因子，可在各种疾病（包括哮喘和特应性皮炎）中诱导 2 型炎症。越来越多的证据表明，TSLP 可以直接刺激多种免疫细胞，例如树突状细胞 (DC)、嗜碱性粒细胞、T 细胞和第 2 组先天性淋巴样细胞 (ILC2)。然而，哪些细胞类型在体内直接响应 TSLP 以及 TSLP 如何引发 2 型炎症仍存在争议。为了确定 TSLP 在体内的确切作用，我们首次生成了多个细胞谱系特异性 TSLP 受体缺陷小鼠，以系统地剖析肺部 2 型炎症中 TSLP 反应性的细胞内在要求。在木瓜蛋白酶诱导的先天免疫介导的 2 型气道炎症中，TSLP 直接刺激 ILC2，但不刺激嗜碱性粒细胞，导致增强的 2 型炎症。另一方面，在 OVA 诱导的适应性免疫介导的 2 型气道炎症中，TSLP 在致敏阶段主要作用于 DC 和 CD4 + T 细胞，而不是嗜碱性粒细胞或 ILC2，并促进 Th2 细胞介导的气道炎症的发展. 总之，这些发现表明 TSLP 在先天性和适应性免疫介导的 2 型炎症的背景下激活不同的免疫细胞级联。