免疫学
过继性细胞移植
细胞凋亡
心肌梗塞
医学
白喉毒素
先天性淋巴细胞
生物
内科学
作者
Tianxiao Liu,Zhaojie Meng,Jing Liu,Jie Li,Yuanyuan Zhang,Zhiyong Deng,Songyuan Luo,Minjie Wang,Qin Huang,Shuya Zhang,Pauline Fendt,Julie Devouassoux,Dazhu Li,Andrew Neil James McKenzie,Matthias Nahrendorf,Peter Libby,Junli Guo,Guo-Ping Shi
出处
期刊:Cardiovascular Research
[Oxford University Press]
日期:2022-09-05
摘要
ABSTRACT Aims Group 2 innate lymphoid cells (ILC2) 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 Rorafl/flIl7rCre/+ mice and in Icosfl-DTR-fl/+Cd4Cre/+ 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+Ly6Chi 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 Rorafl/flIl7rCre/+ mice showed thinner and larger infarcts and more collagen-I depositions than the Il7rCre/+ mice only at early time points post-MI. Mechanistic studies revealed elevated blood IL5 in Il7rCre/+ mice at 1, 7, and 28 days post-MI. Such increase was blunted in Rorafl/flIl7rCre/+ mice. Administration of recombinant IL5 reversed EOS losses in Rorafl/flIl7rCre/+ 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 Rorafl/flIl7rCre/+ 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-induced cardiac fibroblast Smad signaling. Conclusion This study revealed an indirect cardiac reparative role of ILC2 in post-MI hearts via the IL5, EOS, and DC mechanism.
科研通智能强力驱动
Strongly Powered by AbleSci AI