Department of Respiratory, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Science, Jinan, China.
Inflammation. 2022 Apr;45(2):904-918. doi: 10.1007/s10753-021-01594-w. Epub 2021 Nov 10.
Asthma is a chronic disease closely related to airway inflammation. It has been proven that type 2 innate lymphoid cells (ILC2s) play an essential role in airway inflammation in asthma. Furthermore, there is growing evidence that Follistatin-like 1 (FSTL1) can participate in various inflammatory reactions mediated by the JAK/STAT signaling pathway, among others. Therefore, we put forward a new hypothesis: FSTL1 promotes asthmatic airway inflammation by activating ILC2. This study generated an ovalbumin-sensitized asthma model in C57BL/6 and Fstl1 mice. The results showed that the absolute number and the proportion of ILC2 in the ovalbumin-challenged Fstl1 group were lower than in the ovalbumin-challenged wild-type group. We also measured the levels of Th2-type cytokines in the serum and bronchoalveolar lavage fluid (BALF) of mice and found that the corresponding cytokines in the Fstl1 were lower than in the wild-type groups. Finally, we tested whether MEK-JAK-STAT-GATA3 is the specific pathway for FSTL1 to activate ILC2, and further tested our working hypothesis by adding various inhibitors of proteins from this pathway. Overall, these findings reveal that FSTL1 can activate ILC2 through MEK-JAK-STAT-GATA3 to promote airway inflammation and participate in the pathogenesis of asthma.
哮喘是一种与气道炎症密切相关的慢性疾病。已经证明，2 型固有淋巴细胞（ILC2）在哮喘的气道炎症中发挥着重要作用。此外，越来越多的证据表明，卵泡抑素样 1（FSTL1）可以通过 JAK/STAT 信号通路等参与多种炎症反应。因此，我们提出了一个新的假设：FSTL1 通过激活 ILC2 促进哮喘气道炎症。本研究在 C57BL/6 和 Fstl1 小鼠中生成了卵清蛋白致敏哮喘模型。结果表明，在卵清蛋白攻击的 Fstl1 组中，ILC2 的绝对数量和比例均低于卵清蛋白攻击的野生型组。我们还测量了小鼠血清和支气管肺泡灌洗液（BALF）中 Th2 型细胞因子的水平，发现 Fstl1 中的相应细胞因子低于野生型组。最后，我们测试了 MEK-JAK-STAT-GATA3 是否是 FSTL1 激活 ILC2 的特定途径，并通过添加该途径中各种蛋白的抑制剂进一步验证了我们的工作假设。总的来说，这些发现表明 FSTL1 可以通过 MEK-JAK-STAT-GATA3 激活 ILC2 来促进气道炎症，并参与哮喘的发病机制。
