Innate Lymphoid Cells Play a Pathogenic Role in Pericarditis
Hee Sun Choi,
Taejoon Won,
Xuezhou Hou,
Guobao Chen,
William Bracamonte-Baran,
Monica V. Talor,
Ivana Jurčová,
Ondrej Szárszoi,
Lenka Čurnova,
Ilja Stříž,
Jody E. Hooper,
Vojtěch Melenovský,
Daniela Čiháková
Affiliations
Hee Sun Choi
Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
Taejoon Won
Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
Xuezhou Hou
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
Guobao Chen
Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
William Bracamonte-Baran
Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
Monica V. Talor
Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
Ivana Jurčová
Department of Cardiology, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic
Ondrej Szárszoi
Department of Cardiovascular Surgery, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic
Lenka Čurnova
Department of Clinical and Transplant Immunology, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic
Ilja Stříž
Department of Clinical and Transplant Immunology, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic
Jody E. Hooper
Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
Vojtěch Melenovský
Department of Cardiology, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic
Daniela Čiháková
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; Corresponding author
Summary: 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. : Choi et al. show a pathogenic role for innate lymphoid cells (ILCs) in IL-33-induced eosinophilic pericarditis. ILCs are required for the development of pericarditis, and group 2 ILCs (ILC2s) promote the expression of eotaxin by cardiac fibroblasts. In humans, ILCs are found higher in the pericardial fluid of patients with pericarditis compared to others. Keywords: Innate lymphoid cells, group 2 innate lymphoid cells, IL-33, pericarditis, cardiac inflammation, eosinophils, mediastinum, serosal cavity
