Heterogeneity and clonal relationships of adaptive immune cells in ulcerative colitis revealed by single-cell analyses.
Brigid S BolandZhaoren HeMatthew S TsaiJocelyn G OlveraKyla D OmilusikHan G DuongEleanor S KimAbigail E LimaryWenhao JinJ Justin MilnerBingfei YuShefali A PatelTiani L LouisTiffani TyslNadia S KurdAlexandra BortnickLauren K QuezadaJad N KanbarAra MirallesDanny HuylebroeckMark A ValasekParambir S DulaiSiddharth SinghLi-Fan LuJack D BuiCornelis MurreWilliam J SandbornAnanda W GoldrathGene W YeoJohn T ChangPublished in: Science immunology (2021)
Inflammatory bowel disease (IBD) encompasses a spectrum of gastrointestinal disorders driven by dysregulated immune responses against gut microbiota. We integrated single-cell RNA and antigen receptor sequencing to elucidate key components, cellular states, and clonal relationships of the peripheral and gastrointestinal mucosal immune systems in health and ulcerative colitis (UC). UC was associated with an increase in IgG1+ plasma cells in colonic tissue, increased colonic regulatory T cells characterized by elevated expression of the transcription factor ZEB2, and an enrichment of a γδ T cell subset in the peripheral blood. Moreover, we observed heterogeneity in CD8+ tissue-resident memory T (TRM) cells in colonic tissue, with four transcriptionally distinct states of differentiation observed across health and disease. In the setting of UC, there was a marked shift of clonally related CD8+ TRM cells toward an inflammatory state, mediated, in part, by increased expression of the T-box transcription factor Eomesodermin. Together, these results provide a detailed atlas of transcriptional changes occurring in adaptive immune cells in the context of UC and suggest a role for CD8+ TRM cells in IBD.
Keyphrases
- ulcerative colitis
- single cell
- transcription factor
- induced apoptosis
- cell cycle arrest
- regulatory t cells
- rna seq
- immune response
- healthcare
- public health
- poor prognosis
- peripheral blood
- mental health
- gene expression
- cell death
- oxidative stress
- high throughput
- cell proliferation
- working memory
- health information
- inflammatory response
- quality improvement
- nk cells
- patient safety
- heat shock