The elusive case of human intraepithelial T cells in gut homeostasis and inflammation

Abstract

The epithelial barrier of the gastrointestinal tract is home to numerous intraepithelial T cells (IETs). IETs are functionally adapted to the mucosal environment and are among the first adaptive immune cells to encounter microbial and dietary antigens. They possess hallmark features of tissue-resident T cells: they are long-lived nonmigratory cells capable of rapidly responding to antigen challenges independent of T cell recruitment from the periphery. Gut-resident T cells have been implicated in the relapsing and remitting course and persisting low-grade inflammation of chronic gastrointestinal diseases, including IBD and coeliac disease. So far, most data IETs have been derived from experimental animal models; however, IETs and the environmental makeup differ between mice and humans. With advances in techniques, the number of human studies has grown exponentially in the past 5 years. Here, we review the literature on the involvement of human IETs in gut homeostasis and inflammation, and how these cells are influenced by the microbiota and dietary antigens. Finally, targeting of IETs in therapeutic interventions is discussed. Broad insight into the function and role of human IETs in gut homeostasis and inflammation is essential to identify future diagnostic, prognostic and therapeutic strategies.

Human Intestinal Mononuclear Phagocytes in Health and Inflammatory Bowel Disease

“…In addition to the skin, the intestine is one of the major interfaces with the external environment; it is in contact with pathogens as well as commensal microbiota and food antigens (Figure 2). To maintain homeostasis, this bodily niche thus requires a balance between immune tolerance and immune responses against pathogens (170)(171)(172)(173)(174)(175)(176)(177)(178)(179)(180)(181)(182). The intestinal epithelium, mainly composed of a single-cell layer of enterocytes, forms a critical continuous physical barrier with tight junctions connecting adjacent cells and regulates selective permeability for luminal content (Figure 2) (183,184).…”

The regulatory effect of Lactobacillus rhamnosus GG on T lymphocyte and the development of intestinal villi in piglets of different periods

“…In fact, it is estimated that 95% of thymocytes die during transportation. Most cell death is due to their low affinity for the self antigen MHC combination encountered on the surface of thymic epithelial cells and their inability to make positive selection (Lutter et al 2018).…”

Revisiting the gut–joint axis: links between gut inflammation and spondyloarthritis

“…Many of these type 3 immune cells are also altered in the blood and mucosal tissue of patients with IBD 107,108 . CD8 + T cells in the epithelia (intraepithelial lymphocytes; IELs), which also have a type 3 immune phenotype 109 , are particularly important in promoting barrier integrity 110 .…”

“…These cells have been termed tissue-resident memory T cells. CD8 + IELs have the hallmarks of resident memory T cells 109 , namely expression of CD69 and CD103 (αE integrin) and long-term retention in tissue after activation. The localization of IELs in a specific tissue and their prevalence in the small intestine 129 is hypothesized to be responsible for the pattern of lesions in Crohn's disease, and their longevity is thought to be responsible for site-specific flares 130 .…”