Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of T17 cell immunity.

Regulatory T cells (T cells) are instrumental in establishing immunological tolerance. However, the precise effector mechanisms by which T cells control a specific type of immune response in a given tissue remains unresolved. By simultaneously studying T cells from different tissue origins under systemic autoimmunity, in the present study we show that interleukin (IL)-27 is specifically produced by intestinal T cells to regulate helper T17 cell (T17 cell) immunity.

Identification of CD8 + T-Cell-Immune Cell Communications in Ileal Crohn's Disease.

Introduction: Crohn's disease (CD) is a major subtype of inflammatory bowel disease (IBD), a spectrum of chronic intestinal disorders caused by dysregulated immune responses to gut microbiota. Although transcriptional and functional changes in a number of immune cell types have been implicated in the pathogenesis of IBD, the cellular interactions and signals that drive these changes have been less well-studied.

Methods: We performed Cellular Indexing of Transcriptomes and Epitopes by sequencing on peripheral blood, colon, and ileal immune cells derived from healthy subjects and patients with CD.

Small intestine and colon tissue-resident memory CD8 T cells exhibit molecular heterogeneity and differential dependence on Eomes.

Tissue-resident memory CD8 T (T) cells are a subset of memory T cells that play a critical role in limiting early pathogen spread and controlling infection. T cells exhibit differences across tissues, but their potential heterogeneity among distinct anatomic compartments within the small intestine and colon has not been well recognized. Here, by analyzing T cells from the lamina propria and epithelial compartments of the small intestine and colon, we showed that intestinal T cells exhibited distinctive patterns of cytokine and granzyme expression along with substantial transcriptional, epigenetic, and functional heterogeneity.

Heterogeneity and clonal relationships of adaptive immune cells in ulcerative colitis revealed by single-cell analyses.

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.