Choi Hee Sun, Won Taejoon, Hou Xuezhou, Chen Guobao, Bracamonte-Baran William, Talor Monica V, Jurčová Ivana, Szárszoi Ondrej, Čurnova Lenka, Stříž Ilja, Hooper Jody E, Melenovský Vojtěch, Čiháková Daniela
Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Cell Rep. 2020 Mar 3;30(9):2989-3003.e6. doi: 10.1016/j.celrep.2020.02.040.
We find that cardiac group 2 innate lymphoid cells (ILC2s) are essential for the development of IL-33-induced eosinophilic pericarditis. We show a pathogenic role for ILC2s in cardiac inflammation, in which ILC2s activated by IL-33 drive the development of eosinophilic pericarditis in collaboration with cardiac fibroblasts. ILCs, not T and B cells, are required for the development of pericarditis. ILC2s transferred to the heart of Rag2Il2rg mice restore their susceptibility to eosinophil infiltration. Moreover, ILC2s direct cardiac fibroblasts to produce eotaxin-1. We also find that eosinophils reside in the mediastinal cavity and that eosinophils transferred to the mediastinal cavity of eosinophil-deficient ΔdblGATA1 mice following IL-33 treatment migrate to the heart. Thus, the serous cavities may serve as a reservoir of cardiac-infiltrating eosinophils. In humans, patients with pericarditis show higher amounts of ILCs in pericardial fluid than do healthy controls and patients with other cardiac diseases. We demonstrate that ILCs play a critical role in pericarditis.
我们发现心脏2型固有淋巴细胞（ILC2s）对于白细胞介素-33（IL-33）诱导的嗜酸性心包炎的发展至关重要。我们展示了ILC2s在心脏炎症中的致病作用，其中被IL-33激活的ILC2s与心脏成纤维细胞协同推动嗜酸性心包炎的发展。心包炎的发展需要ILCs，而非T细胞和B细胞。转移至Rag2Il2rg小鼠心脏的ILC2s恢复了它们对嗜酸性粒细胞浸润的易感性。此外，ILC2s指导心脏成纤维细胞产生嗜酸性粒细胞趋化因子-1。我们还发现嗜酸性粒细胞存在于纵隔腔中，并且在IL-33处理后转移至嗜酸性粒细胞缺陷的ΔdblGATA1小鼠纵隔腔的嗜酸性粒细胞会迁移至心脏。因此，浆膜腔可能作为心脏浸润嗜酸性粒细胞的储存库。在人类中，心包炎患者心包液中的ILCs含量高于健康对照者和其他心脏病患者。我们证明ILCs在心包炎中起关键作用。
