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Atlas of colonic CD8+ T cells in UC
Corridoni D, Antanaviciute A, Gupta T, et al. Single-cell atlas of colonic CD8+ T cells in ulcerative colitis. Nat Med 2020;26:1480–90.
The aetiology of UC remains unclear but the immune system undoubtedly has a central role in the pathogenesis. The colonic mucosa lamina propria contains an abundance of tissue resident CD8+ T cells. Their transcriptional regulation, effector function and how they dynamically remodel to influence inflammation in IBD remain poorly characterised.
This study profiled CD8+ T cells from three healthy volunteers and compared these with patients with UC using single drop, single cell RNA sequencing. They then linked this with T cell receptor analysis to help define functional relationships and crosstalk with epithelial cell subtypes. They used various techniques to study CD8+ T cells to include gene expression data and gene ontology enrichment analysis followed by area under the receiver operating characteristic curve analysis.
The key findings of this paper highlighted extensive heterogeneity in CD8+ T cell composition, including expanded effector and posteffector terminally differentiated CD8+ T cells. Furthermore, they found that UC-associated CD8+ effector T cells can trigger tissue destruction and produce tumour necrosis factor (TNF)-α. Furthermore, the posteffector cells acquire innate signatures to adopt regulatory functions that may mitigate excessive inflammation. Other key findings included observations that interleukin-26+ (IL-26+) CD8+ cells demonstrated features of chronic stimulation displaying a colitis-specific ETS variant transcription factor 7 transcriptional network that limits inflammation through inhibition of ETS proto-oncogene 1 (ETS1)-controlled genes. The authors summarised that an imbalance between granzyme K+ TNF+ effectors and immunoregulatory IL-26++ may facilitate tissue destruction that manifests as UC. They demonstrated that IL-26 attenuates the severity of colitis when tested in a rodent model but this would require more exploration in IBD human populations.
IFN signalling preserves the stemness of intestinal stem cells
Sato T, Ishikawa S, Asano J et al. Regulated IFN signalling preserves …
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; internally peer reviewed.
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