Inflammatory Memory in Epidermal Stem Cells - A New Strategy for Recurrent Inflammatory Skin Diseases

Abstract

The ability of the skin to "remember" has been a potential mechanism for studying recurrent skin diseases. While it has been thought that the ability to retain past encounters is the prerogative of immune cells, it has recently been discovered that skin tissue stem cells can also take on this task. Epithelial stem cells undergoing inflammation retain their "memory" through epigenetic reprogramming and exhibit rapid epithelialization and epidermal proliferation upon secondary stimulation. This is a non-specific memory modality independent of conventional immune memory, in which histone modifications (acetylation and methylation) and specific transcription factors (AP-1 and STAT3) are involved in the establishment of inflammatory memories, and AIM2/Caspase-1/IL-1β mainly performs the rapid effects of memory. This finding is intriguing for addressing recurrent inflammatory skin diseases, which may explain the fixed-site recurrence of inflammatory skin diseases and develop new therapeutic strategies in the future. However, more research is still needed to decipher the mysteries of memory.

Keywords: epigenetics; inflammatory memory; recurrent inflammatory skin diseases; skin tissue stem cells.

Figure 1

Mechanisms of inflammatory memory in epidermal stem cells. Epidermal stem cells undergoing inflammatory stimulation establish epigenetic memory by regulating chromatin accessibility through histone modifications (H3K4me1, H3K27ac) and the binding of specific transcription factors (AP-1, STAT3); after inflammation subsides, homeostatic transcription factors and JUN are involved in inflammatory memory; and upon secondary stimulation, FOS rapidly bind to the memory domains and reactivate transcription.

Figure 2

Mechanism of inflammatory memory effects; upon secondary stimulation, due to histone modification and transcription factor binding to keep chromatin in an accessible state, memory domain genes are rapidly expressed, of which AIM2 is the main expressed gene, and its downstream AIM2/Caspase-1/IL-1β signaling axis performs cell proliferation effects.