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 Rag2-/-Il2rg-/- 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.

Department of Cardiology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Cardiovascular Surgery Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Clinical and Transplant Immunology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Pathology School of Medicine Johns Hopkins University Baltimore MD 21205 USA

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

W Harry Feinstone Department of Molecular Microbiology and Immunology Bloomberg School of Public Health Johns Hopkins University Baltimore MD 21205 USA

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The protective role of GATA6+ pericardial macrophages in pericardial inflammation