Development, Homeostasis, and Functions of Intestinal Intraepithelial Lymphocytes

Kaer, Luc Van; Olivares–Villagómez, Danyvid

doi:10.4049/jimmunol.1701704

Cited by 84 publications

(91 citation statements)

References 151 publications

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“…They maintain epithelial integrity by promoting re-growth of healthy intestinal epithelial cells following cytolysis of epithelial cells during viral infection. They release interferon gamma (IFN-γ) and TNF-α as a response to an infection, which stimulate inflammation and intestinal barrier dysfunction [29,30].…”

Section: Adaptive Immunitymentioning

confidence: 99%

Intestinal Permeability, Inflammation and the Role of Nutrients

et al. 2020

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The interaction between host and external environment mainly occurs in the gastrointestinal tract, where the mucosal barrier has a critical role in many physiologic functions ranging from digestion, absorption, and metabolism. This barrier allows the passage and absorption of nutrients, but at the same time, it must regulate the contact between luminal antigens and the immune system, confining undesirable products to the lumen. Diet is an important regulator of the mucosal barrier, and the cross-talk among dietary factors, the immune system, and microbiota is crucial for the modulation of intestinal permeability and for the maintenance of gastrointestinal tract (GI) homeostasis. In the present review, we will discuss the role of a number of dietary nutrients that have been proposed as regulators of inflammation and epithelial barrier function. We will also consider the metabolic function of the microbiota, which is capable of elaborating the diverse nutrients and synthesizing products of great interest. Better knowledge of the influence of dietary nutrients on inflammation and barrier function can be important for the future development of new therapeutic approaches for patients with mucosal barrier dysfunction, a critical factor in the pathogenesis of many GI and non-GI diseases.

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Section: Adaptive Immunitymentioning

confidence: 99%

Intestinal Permeability, Inflammation and the Role of Nutrients

et al. 2020

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“… 12 , 13 Conversely, T-IEL are also cytotoxic cells that patrol the epithelial layer to sense and eliminate infected/damaged epithelial cells. 14 They are activated in response to oral infections with pathogens such as Salmonella, 15 , 16 Rotavirus, 17 and Toxoplasma gondii, 18 and at least in the context of loss of γδ T-IEL function, they appear to restrict pathogen entry. 15 , 16 , 19 , 20 Given their constant exposure to the gut microenvironment they must have the capacity to tolerate commensal bacteria while also being able to quickly recognize and fight enteric pathogens.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of activation of innate-like intraepithelial T lymphocytes

2020

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Intraepithelial T lymphocytes (T-IEL) contain subsets of innate-like T cells that evoke innate and adaptive immune responses to provide rapid protection at epithelial barrier sites. In the intestine, T-IEL express variable T cell antigen receptors (TCR), with unknown antigen specificities. Intriguingly, they also express multiple inhibitory receptors, many of which are normally found on exhausted or antigen-experienced T cells. This pattern suggests that T-IEL are antigen-experienced, yet it is not clear where, and in what context, T-IEL encounter TCR ligands. We review recent evidence indicating TCR antigens for intestinal innate-like T-IEL are found on thymic or intestinal epithelium, driving agonist selection of T-IEL. We explore the contributions of the TCR and various costimulatory and co-inhibitory receptors in activating T-IEL effector functions. The balance between inhibitory and activating signals may be key to keeping these highly cytotoxic, rapidly activated cells in check, and key to harnessing their immune surveillance potential.

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“…The mechanisms underlying gliadin‐mediated activation of the adaptive immune response are relatively well defined in CD, but the nature and regulation of the innate immune response within the epithelial compartment is not fully understood . Intraepithelial lymphocytes (IELs) constitute a diverse population, including thymus‐derived T cells of the αβ and γδ lineage and subsets of bone marrow‐derived innate lymphoid cells (ILCs) . It has been shown that IELs, specifically cytotoxic T cell receptor (TCR)‐αβ + T cells, which undergo natural killer (NK)‐like reprogramming on interacting with epithelial stress‐induced ligands, and IL‐15, up‐regulated upon exposure to toxic gliadin peptides, promote epithelial destruction .…”

Section: Introductionmentioning

confidence: 99%

“…Contributions of other types of lymphoid cells to the innate immune response in CD are suspected, but these are currently unclear . Recent studies have implicated ILCs in the pathogenesis of a variety of intestinal inflammatory disorders ; however, data regarding the repertoire of human proximal small intestinal (SI) ILCs and their alterations in CD are limited .…”

Section: Introductionmentioning

confidence: 99%

Phenotypic shift of small intestinal intra-epithelial type 1 innate lymphoid cells in celiac disease is associated with enhanced cytotoxic potential

Uhde

Bunin

et al. 2020

Clinical &Amp; Experimental Immunology

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The small intestinal (SI) epithelium harbors a heterogeneous population of lymphocytes that mediate mucosal damage and repair in celiac disease (CD). The composition and roles of human proximal SI intra-epithelial innate lymphoid cells (ILCs), and their alterations in CD, are not well understood. We report that duodenal intra-epithelial ILCs predominantly consist of natural killer (NK)p44 + CD127 − cytotoxic ILC1s and NKp44 − CD127 + helper ILC1s, while ILC3s only represent a minor population. In patients with newly diagnosed or active CD (ACD) and refractory CD type 1 (RCD I), the frequency of SI NKp44 + ILCs is decreased, with restoration of NKp44 + ILC frequency observed in patients adhering to a gluten-free diet who show evidence of mucosal healing. Moreover, the frequency of SI NKp44 − ILCs is increased in ACD and RCD I patients and correlates with the severity of villous atrophy and epithelial damage, as assessed by serum levels of fatty acid binding protein 2 (FABP2). We show that the ILC alterations in CD represent a phenotypic shift of cytotoxic ILC1s rather than an increase in helper ILC1s or transdifferentiation of ILC1s to ILC3s, and activation-induced loss of NKp44 by cytotoxic ILC1s is associated with increased interferon (IFN)-γ expression and release of lytic granules. These findings suggest that intra-epithelial NKp44 − CD127 − cytotoxic ILC1s may contribute to mucosal damage in CD.

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Development, Homeostasis, and Functions of Intestinal Intraepithelial Lymphocytes

Cited by 84 publications

References 151 publications

Intestinal Permeability, Inflammation and the Role of Nutrients

Intestinal Permeability, Inflammation and the Role of Nutrients

Mechanisms of activation of innate-like intraepithelial T lymphocytes

Phenotypic shift of small intestinal intra-epithelial type 1 innate lymphoid cells in celiac disease is associated with enhanced cytotoxic potential

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