Regulatory T‐cell stability and functional plasticity in health and disease
Vanshika Malviya, Lidia Yshii, Steffie Junius, Abhishek D. Garg, Stéphanie Humblet‐Baron, Susan Schlenner
Abstract
Abstract FOXP3‐expressing regulatory T cells (T reg ) are indispensable for immune homeostasis and tolerance, and in addition tissue‐resident T reg have been found to perform noncanonical, tissue‐specific functions. For optimal tolerogenic function during inflammatory disease, T reg are equipped with mechanisms that assure lineage stability. T reg lineage stability is closely linked to the installation and maintenance of a lineage‐specific epigenetic landscape, specifically a T reg ‐specific DNA demethylation pattern. At the same time, for local and directed immune regulation T reg must possess a level of functional plasticity that requires them to partially acquire T helper cell (T H ) transcriptional programs—then referred to as T H ‐like T reg . Unleashing T H programs in T reg , however, is not without risk and may threaten the epigenetic stability of T reg with consequently pathogenic ex‐T reg contributing to (auto‐) inflammatory conditions. Here, we review how the T reg ‐stabilizing epigenetic landscape is installed and maintained, and further discuss the development, necessity and lineage instability risks of T H 1‐, T H 2‐, T H 17‐like T reg and follicular T reg .