Establishment, maintenance, and recall of inflammatory memory

Area of Science:

• Cellular Biology
• Immunology
• Genetics

Background:

• Cells possess an inflammatory memory, enabling rapid responses to secondary stimuli, but the underlying mechanisms are poorly understood.
• This memory is crucial for tissue fitness during health and disease, yet its molecular basis remains elusive.

Purpose of the Study:

• To elucidate the mechanisms by which cells establish, maintain, and recall inflammatory memory.
• To identify key molecular players and dynamic changes involved in inflammatory memory recall.

Main Methods:

• Utilized murine epidermal stem cells as a model system.
• Conducted temporal, dynamic analyses of chromatin accessibility, histone modifications, and transcription factor binding during inflammation, resolution, and memory recall.
• Investigated the roles of transcription factors FOS, JUN, and STAT3.

Main Results:

• Identified a unifying role for the stress-responsive transcription factor FOS in establishing inflammatory memory, partnering with JUN and STAT3.
• Demonstrated that JUN remains on memory domains with homeostatic factors, facilitating rapid FOS re-recruitment and gene activation upon secondary challenges.
• Uncovered dynamic changes in chromatin and transcription factor binding that underpin memory formation and recall.

Conclusions:

• Proposed a comprehensive mechanism for inflammatory memory and recall, centered on the interplay of FOS, JUN, and STAT3.
• Highlighted the significance of these findings for understanding tissue responses to inflammation and injury.
• Suggests potential universal applicability of the identified mechanism across different cell types and stimuli.