Inflammatory Memory Sensitizes Skin Epithelial Stem Cells to Tissue Damage
By S. Naik, Samantha B. Larsen, Nicholas C. Gomez, Kirill Alaverdyan, Ataman Sendoel, S. Yuan, Lisa Polak, Anita Kulukian, Sophia Chai, Elaine Fuchs. Nature, 2017
627 citations recorded by the source corpus.
The skin barrier is the body’s first line of defence against environmental assaults, and is maintained by epithelial stem cells (EpSCs). Despite the vulnerability of EpSCs to inflammatory pressures, neither the primary response to inflammation nor its enduring consequences are well understood. Here we report a prolonged memory to acute inflammation that enables mouse EpSCs to hasten barrier restoration after subsequent tissue damage. This functional adaptation does not require skin-resident macrophages or T cells. Instead, EpSCs maintain chromosomal accessibility at key stress response genes that are activated by the primary stimulus. Upon a secondary challenge, genes governed by these domains are transcribed rapidly. Fuelling this memory is Aim2, which encodes an activator of the inflammasome. The absence of AIM2 or its downstream effectors, caspase-1 and interleukin-1β, erases the ability of EpSCs to recollect inflammation. Although EpSCs benefit from inflammatory tuning by heightening their responsiveness to subsequent stressors, this enhanced sensitivity probably increases their susceptibility to autoimmune and hyperproliferative disorders, including cancer.
Subfields: Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/11e45d8207af112fa65908254c25b1b1c4e954fb
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Citations in the corpus
- The IL-17 family of cytokines in health and disease (2019, background): “Skin that has previously been inflamed in a psoriasis-like model shows more rapid wound closure that is partially dependent on RORγt+ T cells (and by inference IL-17) (Naik et al., 2017).”
- Cellular and molecular mechanisms of skin wound healing (2024, neutral): “Epigenetic changes also underpin a newly described phenomenon of inflammatory memory exhibited by stem cells at an epidermal wound edge, enabling them to respond more rapidly to wound activators upon secondary exposure to stress signals 27–30 .”
- Fibroblasts: origins, definitions, and functions in health and disease (2021, background): “Future work is needed to determine whether different fibroblast pools harbor distinct levels of latent plasticity and whether fibroblasts retain an epigenetic memory of earlier reparative events that heightens their responsiveness to subsequent insults, as seen in epithelial cells (Naik et al., 2017”