The role of innate lymphoid cells in the heart and cardiac inflammation

To investigate the role of innate lymphoid cells (ILCs) in the heart, we have established a pericarditis model in which mice develop pericarditis upon IL-33 injections. Studies have shown the role of group 2 innate lymphoid cells (ILC2s) mostly in mucosal organs such as lung and gut, however, the role of ILC2s in the heart has been overlooked. We found that the number of ILC2s increases in the heart after IL-33 treatment. The aim of this work is to examine the role of ILC2s in inflammatory heart disease using the IL-33-induced pericarditis model. We hypothesize that IL-33 induces cardiac resident ILCs to become activated ILC2s to produce large amounts of IL-5 and IL-13, driving the development of pericarditis. To determine whether ILCs are required for pericarditis development, we compared WT mice to Rag2 −/− mice and to Rag2 −/− γc −/− mice which lack all of lymphoid cells including ILCs. Whereas Rag2 −/− mice developed pericarditis, Rag2 −/− γc −/− mice were completely protected. This indicates that the adaptive immune response is not required for the development of IL-33-induced pericarditis, but ILCs may play a pathogenic role. We assessed cytokine production by ILC2s in pericarditis to determine the function of ILC2s in the heart. Cardiac ILC2s were a major source of IL-5 and IL-13. The number of eosinophils in the heart was significantly reduced by anti-IL-5 treatment, which prevented the development of pericarditis. In addition, IL-13 −/− mice developed less severe pericarditis compared to WT mice. These data suggest that ILCs play a critical role in inflammatory heart diseases. The pathogenic mechanism of ILC2s in the heart could provide insight into novel therapeutic strategies for treating cardiac inflammation including pericarditis.