Immunoregulatory function of human intestinal mucosa lymphoid cells: evidence for enhanced suppressor cell activity in inflammatory bowel disease.

Abstract The intestinal mucosa represents a unique environment where the coordinated function of diverse epithelial, mesenchymal, and immune cells maintains a physiologically balanced environment in the presence of gut microbiota. The intestinal mucosa plays a central role in the pathogenesis of inflammatory bowel disease (IBD), yet the molecular and cellular composition of this diverse environment is poorly understood. However, the recent advent of multimodal single-cell technologies, including single-cell RNA sequencing (scRNA-seq), now provides an opportunity to accurately map the tissue architecture, characterize rare cell types that were previously overlooked, and define function at a single-cell level. In this review, we summarize key advances in single-cell technology and provide an overview of important aspects of computational analysis. We describe emerging data in the field of IBD and discuss how the characterization of novel intestinal mucosa cell populations is reshaping our understanding of this complex disease. We conclude by considering the potential clinical applications, including the definition of novel drug targets and the opportunity for personalization of care in this exciting new era of precision medicine.

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Characterization of γδ T Cells in Intestinal Mucosa From Patients With Early-Onset or Long-Standing Inflammatory Bowel Disease and Their Correlation With Clinical Status

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz015 ◽

2019 ◽

Vol 13 (7) ◽

pp. 873-883 ◽

Cited By ~ 5

Author(s):

Elena Lo Presti ◽

Roberto Di Mitri ◽

Filippo Mocciaro ◽

Anna Barbara Di Stefano ◽

Nunzia Scibetta ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

T Cells ◽

Intestinal Mucosa ◽

Bowel Disease ◽

Early Onset ◽

Γδ T Cells ◽

Healthy Tissue ◽

Effector Memory ◽

Tnf Α ◽

Inflammatory Bowel

Abstract Background and Aims Inflammatory bowel disease [IBD] is a complex chronic inflammatory disease of the human gut with no clear aetiology. Traditionally, dysregulated adaptive immune responses play an important role even though accumulating evidence suggests a role also for innate immunity. Because of the well-known plasticity of γδ T cells, we investigated their percentage occurrence, phenotypic features and effector functions in the intestinal mucosa of early-onset and long-standing IBD patients, as compared to healthy subjects. Methods Fresh biopsies from 30 Crohn’s disease and ulcerative colitis patients were obtained and digested, and cells were analysed by flow cytometry. Results We found a reduced frequency of Vδ1 T cells in tissue from early and late IBD patients (2.24% and 1.95%, respectively, vs 5.44% in healthy tissue) but an increased frequency of Vδ2 T cells in the gut of late IBD patients (3.19% in late patients vs 1.5% in early patients and 1.65% in healthy tissue). The infiltrating Vδ2 T cells had predominant effector memory and terminally differentiated phenotypes and produced elevated levels of tumour necrosis factor-α [TNF-α] and interleukin-17 [IL-17]. The frequency of tissue Vδ2 T cells correlated with the extent of the inflammatory response and the severity of IBD. Conclusion Our study shows that tissue Vδ1 T cells are decreased in IBD patients while Vδ2 T cells are increased in the gut of IBD patients and contribute to TNF-α production. Moreover, we identify an as yet unappreciated role of Vδ2 T cells in IL-17 production in the gut of long-standing IBD patients, suggesting that they also participate in the chronic inflammatory process.

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