Group 2 innate lymphoid cells protect mouse heart from myocardial infarction injury via interleukin 5, eosinophils, and dendritic cells. Issue 4 (5th September 2022)

• Record Type: Journal Article
• Authors: Liu, Tianxiao; Meng, Zhaojie; Liu, Jing; Li, Jie; Zhang, Yuanyuan; Deng, Zhiyong; Luo, Songyuan; Wang, Minjie; Huang, Qin; Zhang, Shuya; Fendt, Pauline; Devouassoux, Julie; Li, Dazhu; McKenzie, Andrew Neil James; Nahrendorf, Matthias; Libby, Peter; Guo, Junli; Shi, Guo-Ping
• Is Part Of: Cardiovascular research. Volume 119:Issue 4(2023)
• Page Start: 1046
• Page End: 1061
• Publication Date: 2022-09-05
• Subjects: ILC2 -- myocardial infarction -- interleukin 5 -- eosinophil -- dendritic cell; Cardiovascular system -- Diseases -- Periodicals; Cardiovascular system -- Periodicals; 616.1
• DOI: 10.1093/cvr/cvac144
• Languages: English
• ISSNs: 0008-6363

Abstract

Abstract: Aims: Group 2 innate lymphoid cells (ILC2s) regulate adaptive and innate immunities. In mouse heart, production of myocardial infarction (MI) increased ILC2 accumulation, suggesting a role for ILC2 in cardiac dysfunction post-MI. Methods and results: We produced MI in ILC2-deficeint Rora fl/fl Il7r Cre/+ mice and in Icos fl-DTR-fl/+ Cd4 Cre/+ mice that allowed diphtheria toxin-induced ILC2 depletion. Genetic or induced deficiency of ILC2 in mice exacerbated cardiac dysfunction post-MI injury along with increased myocardial accumulation of neutrophils, CD11b + Ly6C hi monocytes, and CD4 + T cells but deficiency of eosinophils (EOS) and dendritic cells (DC). Post-MI hearts from genetic and induced ILC2-deficient mice contained many more apoptotic cells than those of control mice, and Rora fl/fl Il7r Cre/+ mice showed thinner and larger infarcts and more collagen-I depositions than the Il7r Cre/+ mice only at early time points post-MI. Mechanistic studies revealed elevated blood IL5 in Il7r Cre/+ mice at 1, 7, and 28 days post-MI. Such increase was blunted in Rora fl/fl Il7r Cre/+ mice. Administration of recombinant IL5 reversed EOS losses in Rora fl/fl Il7r Cre/+ mice, but IL5 did not correct the DC loss in these mice. Adoptive transfer of ILC2, EOS, or DC from wild-type mice, but not ILC2 from Il5 −/− mice improved post-MI cardiac functions in Rora fl/fl Il7r Cre/+ recipient mice. EOS are known to protect cardiomyocytes from apoptosis. Here we showed that DC acted like EOS in blocking cardiomyocyte apoptosis. Yet, ILC2 or IL5 alone did not directly affect cardiomyocyte apoptosis or TGF-β (transforming growth factor-β)-induced cardiac fibroblast Smad signalling. Conclusion: This study revealed an indirect cardiac reparative role of ILC2 in post-MI hearts via the IL5, EOS, and DC mechanism. Graphical Abstract: Graphical abstract