An emerging role of regulatory T-cells in cardiovascular repair and regeneration

Abstract

Accumulating evidence has demonstrated that immune cells play an important role in the regulation of tissue repair and regeneration. After injury, danger signals released by the damaged tissue trigger the initial pro-inflammatory phase essential for removing pathogens or cellular debris that is later replaced by the anti-inflammatory phase responsible for tissue healing. On the other hand, impaired immune regulation can lead to excessive scarring and fibrosis that could be detrimental for the restoration of organ function. Regulatory T-cells (Treg) have been revealed as the master regulator of the immune system that have both the immune and regenerative functions. In this review, we will summarize their immune role in the induction and maintenance of self-tolerance; as well as their regenerative role in directing tissue specific response for repair and regeneration. The latter is clearly demonstrated when Treg enhance the differentiation of stem or progenitor cells such as satellite cells to replace the damaged skeletal muscle, as well as the proliferation of parenchymal cells including neonatal cardiomyocytes for functional regeneration. Moreover, we will also discuss the reparative and regenerative role of Treg with a particular focus on blood vessels and cardiac tissues. Last but not least, we will describe the ongoing clinical trials with Treg in the treatment of autoimmune diseases that could give clinically relevant insights into the development of Treg therapy targeting tissue repair and regeneration.

Effects of prenatal photobiomodulation treatment on neonatal hypoxic ischemia in rat offspring

“…Furthermore, myeloid cell activation after neonatal HIE has been well-documented 111 , 112 . The M1 pro-inflammatory macrophage phenotype is associated with increased production of pro-inflammatory cytokines 113 - 116 , and the M2 anti-inflammatory macrophage phenotype is related to tissue repair, phagocytosis of protein aggregates, and removal of cellular debris 117 , 118 . An M1/M2 polarization has been shown to play an important role in HIE pathophysiological development 119 .…”

Macrophage Polarization in Cardiac Tissue Repair Following Myocardial Infarction

“…It is important to mention that immune cells have different effects on macrophage polarization in immature hearts compared to adult cardiac tissue. Thus, it was generally accepted that T regs promote M2 phenotypes in an adult heart [ 98 ]. However, recently, Li and colleagues demonstrated that in neonatal hearts, T regs suppress the activation of M2 macrophages and inhibit fibrosis [ 99 ].…”

The Cross-Talk between Mesenchymal Stem Cells and Immune Cells in Tissue Repair and Regeneration

“…In addition to their immunosuppressive properties, Tregs mediate tissue repair by synthesizing “pro-repair” molecules, such as AREG and keratinocyte growth factor (KGF) that directly promote tissue regeneration [ 31 , 35 , 36 ]. KGF secreted by activated Tregs promotes alveolar epithelial repair, while Treg-derived AREG, an epidermal growth factor receptor (EGFR) ligand, induces mitogenic and cell differentiation signals, enabling reparation of injured muscles, lungs and colons by promoting differentiation of tissue resident stem cells and progenitor cells [ 31 , 35 , 36 , 37 ]. Additionally, Tregs may promote tissue regeneration by inducing the proliferation of endothelial and parenchymal cells [ 38 , 39 ].…”