Neonatal T-reg cells promote cardiac repair and limit fibrosis post-injury via Rcn3, enhancing recovery and anti-fibrotic effects compared to adults.
Does Rcn3 expression in neonatal regulatory T cells mediate anti-fibrotic effects and contribute to cardiac repair after myocardial infarction?
Neonatal regulatory T cells promote cardiac repair and limit fibrosis post-myocardial infarction via the Rcn3 gene, identifying a potential therapeutic target for pathological remodeling in adult hearts.
Absolute Event Rate: 0% vs 0%
The neonatal heart possesses a unique capacity for reparative healing after myocardial injury, unlike the adult heart. While immune cells, particularly T cells, regulate post-infarction inflammation, their role in age-dependent cardiac repair remains unclear. This study aimed to characterize the temporal activation of T cell subsets and their contribution to immune homeostasis and myocardial repair. Myocardial infarction was induced in mice of different ages, and T cell subsets (CD4+ T cells, CD8+ T cells, and CD4+Foxp3+ T T-reg cells) were analyzed using flow cytometry and RNA sequencing. Neonatal hearts exhibited CD4+ T cells, CD8+ T cells, and T-reg cells that gradually increased until seven days post-injury. Transcriptome analysis identified Rcn3 as a neonatal-specific, injury-responsive gene in T-reg cells, with minimal induction in adult and aged hearts, promoting a reparative microenvironment and exerting anti-fibrotic effects via the PI3K/Akt pathway. Under endoplasmic reticulum stress, Rcn3 activated unfolded protein response genes, and Rcn3-conditioned media reduced fibrosis-associated gene expression in adult cardiac fibroblasts. In a conditional knockout mouse model (Lck-cre; Rcn3fl/fl), Rcn3 deletion in T cells led to impaired cardiac function recovery and increased fibrosis post-injury. These findings suggest that neonatal T-reg cells play a crucial role in cardiac repair, with Rcn3 as a potential therapeutic target for enhancing immune-mediated cardiac repair and limiting pathological remodeling in the adult heart.
Kino et al. (Thu,) reported a other. Neonatal T-reg cells promote cardiac repair and limit fibrosis post-injury via Rcn3, enhancing recovery and anti-fibrotic effects compared to adults.