Divison of Rheumatology, Allergy and Immunology, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Veterans Affairs San Diego Health Care System, La Jolla, CA, USA.
Nat Commun. 2022 Jul 30;13(1):4435. doi: 10.1038/s41467-022-32176-5.
Innate lymphoid cells (ILC) promote lung inflammation in asthma through cytokine production. RNA-binding proteins (RBPs) are critical post-transcriptional regulators, although less is known about RBPs in ILC biology. Here, we demonstrate that RNA-binding motif 3 (RBM3) is highly expressed in lung ILCs and is further induced by alarmins TSLP and IL-33. Rbm3 and Rbm3Rag2 mice exposed to asthma-associated Alternaria allergen develop enhanced eosinophilic lung inflammation and ILC activation. IL-33 stimulation studies in vivo and in vitro show that RBM3 suppressed lung ILC responses. Further, Rbm3 ILCs from bone marrow chimeric mice display increased ILC cytokine production suggesting an ILC-intrinsic suppressive function of RBM3. RNA-sequencing of Rbm3 lung ILCs demonstrates increased expression of type 2/17 cytokines and cysteinyl leukotriene 1 receptor (CysLT1R). Finally, Rbm3Cyslt1r mice show dependence on CysLT1R for accumulation of ST2IL-17 ILCs. Thus, RBM3 intrinsically regulates lung ILCs during allergen-induced type 2 inflammation that is partially dependent on CysLT1R.
固有淋巴细胞 (ILC) 通过细胞因子产生促进哮喘中的肺部炎症。RNA 结合蛋白 (RBP) 是关键的转录后调节因子，尽管在 ILC 生物学中对 RBP 的了解较少。在这里，我们证明 RNA 结合基序 3 (RBM3) 在肺 ILC 中高度表达，并进一步被警报素 TSLP 和 IL-33 诱导。暴露于与哮喘相关的链格孢过敏原的 Rbm3 和 Rbm3Rag2 小鼠会发展出增强的嗜酸性粒细胞性肺部炎症和 ILC 激活。体内和体外的 IL-33 刺激研究表明，RBM3 抑制了肺 ILC 的反应。此外，来自骨髓嵌合小鼠的 Rbm3 ILC 显示出增加的 ILC 细胞因子产生，表明 RBM3 具有 ILC 内在的抑制功能。Rbm3 肺 ILC 的 RNA 测序表明，2/17 型细胞因子和半胱氨酰白三烯 1 受体 (CysLT1R) 的表达增加。最后，Rbm3Cyslt1r 小鼠显示对 CysLT1R 的依赖性，以积累 ST2IL-17 ILC。因此，RBM3 在过敏原诱导的 2 型炎症期间内在地上调肺 ILC，这部分依赖于 CysLT1R。
