Single-cell profiling reveals unique features of diabetogenic T cells in anti-PD-1-induced type 1 diabetes mice.
Jenna L CollierKristen E PaukenCatherine A A LeeDillon G PattersonSamuel C MarksonThomas S ConwayMegan E FungJoshua A FranceKyla N MucciaroneChristine G LianGeorge F MurphyArlene H SharpePublished in: The Journal of experimental medicine (2023)
Immune-related adverse events (irAEs) are a notable complication of PD-1 cancer immunotherapy. A better understanding of how these iatrogenic diseases compare with naturally arising autoimmune diseases is needed for treatment and monitoring of irAEs. We identified differences in anti-PD-1-induced type 1 diabetes (T1D) and spontaneous T1D in non-obese diabetic (NOD) mice by performing single-cell RNA-seq and TCR-seq on T cells from the pancreas, pancreas-draining lymph node (pLN), and blood of mice with PD-1-induced T1D or spontaneous T1D. In the pancreas, anti-PD-1 resulted in expansion of terminally exhausted/effector-like CD8+ T cells, an increase in T-bethi CD4+FoxP3- T cells, and a decrease in memory CD4+FoxP3- and CD8+ T cells in contrast to spontaneous T1D. Notably, anti-PD-1 caused increased TCR sharing between the pancreas and the periphery. Moreover, T cells in the blood of anti-PD-1-treated mice expressed markers that differed from spontaneous T1D, suggesting that the blood may provide a window to monitor irAEs rather than relying exclusively on the autoimmune target organ.
Keyphrases
- single cell
- rna seq
- type diabetes
- regulatory t cells
- high fat diet induced
- lymph node
- high glucose
- diabetic rats
- drug induced
- high throughput
- magnetic resonance
- metabolic syndrome
- glycemic control
- cardiovascular disease
- insulin resistance
- adipose tissue
- oxidative stress
- dendritic cells
- endothelial cells
- healthcare
- immune response
- squamous cell carcinoma
- neoadjuvant chemotherapy
- social media
- working memory
- weight loss
- newly diagnosed
- health information