作者
Wenfeng Wang,Xiao Li,X. X. Ding,Shanshan Xiong,Zhen-lei Hu,Xuan Lu,Kan Zhang,Heng Zhang,Qianwen Hu,Kaa Seng Lai,Zhongxiang Chen,Junjie Yang,Hejie Song,Ye Wang,Wei Lü,Zeyang Xia,Bin Zhou,Yulong He,Jun Pu,Xiao Liu,Rongqin Ke,Tao Wu,Chuanxin Huang,Antonio Baldini,Min Zhang,Zhen Zhang
摘要
The heart is an autoimmune-prone organ. It is crucial for the heart to keep injury-induced autoimmunity in check to avoid autoimmune-mediated inflammatory disease. However, little is known about how injury-induced autoimmunity is constrained in hearts. Here, we reveal an unknown intramyocardial immunosuppressive program driven by Tbx1, a DiGeorge syndrome disease gene that encodes a T-box transcription factor (TF). We found induced profound lymphangiogenic and immunomodulatory gene expression changes in lymphatic endothelial cells (LECs) after myocardial infarction (MI). The activated LECs penetrated the infarcted area and functioned as intramyocardial immune hubs to increase the numbers of tolerogenic dendritic cells (tDCs) and regulatory T (Treg) cells through the chemokine Ccl21 and integrin Icam1, thereby inhibiting the expansion of autoreactive CD8+ T cells and promoting reparative macrophage expansion to facilitate post-MI repair. Mimicking its timing and implementation may be an additional approach to treating autoimmunity-mediated cardiac diseases.