Lymphatic Endothelial Transcription Factor TBX1 Promotes an Immunosuppressive Microenvironment to Facilitate Post-Myocardial Infarction Repair

Authors

• Shanshan Xiong
• Zhenlei Hu
• Xuan Lu
• Kan Zhang
• Heng Zhang
• Qianwen Hu
• Kaa Seng Lai
• Zhongxiang Chen
• Junjie Yang
• Hejie Song
• Ye Wang
• Lu Wei
• Zeyang Xia
• Bin Zhou
• Yulong He
• Jun Pu
• Xiao Liu
• Rongqin Ke
• Tao Wu
• Chuanxin Huang
• Antonio Baldini
• Min Zhang
• Zhen Zhang

Language

English

Publication Date

10-10-2023

Journal

Immunity

DOI

10.1016/j.immuni.2023.07.019

PMID

37625409

Abstract

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.

Keywords

Animals, T-Box Domain Proteins, Myocardial Infarction, Mice, Dendritic Cells, T-Lymphocytes, Regulatory, Endothelial Cells, Chemokine CCL21, Macrophages, Intercellular Adhesion Molecule-1, Autoimmunity, Immune Tolerance, Lymphangiogenesis, CD8-Positive T-Lymphocytes, Mice, Inbred C57BL, Mice, Knockout, Humans, Myocardium, Cellular Microenvironment, Disease Models, Animal, Male, Tbx1, autoimmunity, cardiac repair, heart, immune suppression, lymphangiogenesis, lymphatic endothelial cells, myocardial infarction

Published Open-Access

yes

Recommended Citation

Xiong, Shanshan; Hu, Zhenlei; Lu, Xuan; et al., "Lymphatic Endothelial Transcription Factor TBX1 Promotes an Immunosuppressive Microenvironment to Facilitate Post-Myocardial Infarction Repair" (2023). Faculty, Staff and Students Publications. 8591.
https://digitalcommons.library.tmc.edu/baylor_docs/8591