Tissue-resident memory CD8 + T cells possess unique transcriptional, epigenetic and functional adaptations to different tissue environments.
John T CrowlMaximilian HeegAmir FerryJ Justin MilnerKyla D OmilusikClara TomaZhaoren HeJohn T ChangAnanda W GoldrathPublished in: Nature immunology (2022)
Tissue-resident memory T cells (T RM cells) provide protective immunity, but the contributions of specific tissue environments to T RM cell differentiation and homeostasis are not well understood. In the present study, the diversity of gene expression and genome accessibility by mouse CD8 + T RM cells from distinct organs that responded to viral infection revealed both shared and tissue-specific transcriptional and epigenetic signatures. T RM cells in the intestine and salivary glands expressed transforming growth factor (TGF)-β-induced genes and were maintained by ongoing TGF-β signaling, whereas those in the fat, kidney and liver were not. Constructing transcriptional-regulatory networks identified the transcriptional repressor Hic1 as a critical regulator of T RM cell differentiation in the small intestine and showed that Hic1 overexpression enhanced T RM cell differentiation and protection from infection. Provision of a framework for understanding how CD8 + T RM cells adapt to distinct tissue environments, and identification of tissue-specific transcriptional regulators mediating these adaptations, inform strategies to boost protective memory responses at sites most vulnerable to infection.
Keyphrases
- gene expression
- transcription factor
- transforming growth factor
- induced apoptosis
- cell cycle arrest
- dna methylation
- epithelial mesenchymal transition
- working memory
- genome wide
- endoplasmic reticulum stress
- patient safety
- adipose tissue
- oxidative stress
- cell proliferation
- high glucose
- single cell
- cell death
- heat shock
- quality improvement
- high intensity
- fatty acid
- pi k akt
- heat stress