Innate Lymphoid Cells Play a Pathogenic Role in Pericarditis

We find that cardiac group 2 innate lymphoid cells (ILC2s) are essential for the development of IL-33- induced eosinophilic pericarditis. We show a patho- genic 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 Rag2?/?Il2rg?/?mice restore their sus- ceptibility 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 medi- astinal cavity of eosinophil-deficient DdblGATA1 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. Wedemon- strate that ILCs play a critical role in pericarditis.