Intestinal intraepithelial lymphocytes: Maintainers of intestinal immune tolerance and regulators of intestinal immunity

Ma, Haitao; Qiu, Yuan; Yang, Hua

doi:10.1002/jlb.3ru0220-111

Cited by 49 publications

(64 citation statements)

References 96 publications

(253 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Intestinal mucosal immunity requires a timely immune response against invading pathogens to maintain intestinal homeostasis and protect the intestine from foreign pathogens. The single layer of intestinal epithelial cells and intraepithelial lymphocytes located between the epithelial cells form the first line of defense against foreign pathogen infection (Kansler and Li, 2019;Ma et al, 2021). Epithelial cells can respond quickly to antigen stimulation and remove foreign pathogens.…”

Section: Discussionmentioning

confidence: 99%

Enterovirus 71 Antagonizes Antiviral Effects of Type III Interferon and Evades the Clearance of Intestinal Intraepithelial Lymphocytes

et al. 2022

View full text Add to dashboard Cite

Enterovirus 71 (EV71) is the major pathogen causing severe neurological complications and hand, foot, and mouth disease. The intestinal mucosal immune system has a complete immune response and immune regulation mechanism, consisting of densely arranged monolayer intestinal epithelial cells (IECs) and intestinal intraepithelial lymphocytes (iIELs) distributed among the IECs, which constitute the first line of intestinal mucosa against infection of foreign pathogens. As an enterovirus, EV71 is transmitted by the intestinal tract; however, the mechanisms it uses to evade the immunosurveillance of the intestinal mucosal immune system are still incompletely clarified. The present study investigated how EV71 evades from recognizing and eliminating IECs, iIELs, and iNK cells. We found that EV71 infection induced a higher level of type III interferons (IFN-λ) than type I interferons (IFN-β) in IECs, and the addition of IFN-λ markedly restricted EV71 replication in IECs. These results indicate that IFN-λ plays a more important role in anti-EV71 intestinal infection. However, EV71 infection could markedly attenuate the antiviral responses of IFN-λ. Mechanistically, 2A protease (2Apro) and 3C protease (3Cpro) of EV71 inhibited the IFN-λ production and IFN-λ receptor expression and further decreased the response of IECs to IFN-λ. In addition, we found that EV71-infected IECs were less susceptible to the lysis of intestinal NK (iNK) cells and CD3+iIELs. We revealed that the viral 2Apro and 3Cpro could significantly reduce the expression of the ligands of natural killer group 2D (NKG2D) and promote the expression of PD-L1 on IECs, rendering them to evade the recognition and killing of iNK and CD3+iIELs. These results provide novel evasion mechanisms of EV71 from intestinal mucosal innate immunity and may give new insights into antiviral therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Enterovirus 71 Antagonizes Antiviral Effects of Type III Interferon and Evades the Clearance of Intestinal Intraepithelial Lymphocytes

et al. 2022

View full text Add to dashboard Cite

show abstract

“…In particular, CD8 αα + TCR αβ + IELs, TCR γδ + IELs, and CD4+ CD8 αα + IELs show great potential in maintaining intestinal immune tolerance and regulating intestinal immunity. However, once the intestinal microenvironment is abnormal or intestinal tolerance is disrupted, intestinal intraepithelial lymphocytes may be abnormally activated and lead to the occurrence of disease [ 38 ]. Of course, there are other immune cells such as mast cells and macrophages that secrete inflammatory mediators, activate complement, increase blood flow, dilate capillaries, increase permeability, and deposit fibrin networks, which are involved in the pathogenesis of CD [ 39 ].…”

Section: The Composition and Function Of The Intestinal Barriermentioning

confidence: 99%

Biological Clock and Inflammatory Bowel Disease Review: From the Standpoint of the Intestinal Barrier

Tian

Zhang

2022

Gastroenterology Research and Practice

View full text Add to dashboard Cite

Inflammatory bowel disease is a group of chronic, recurrent, nonspecific inflammatory diseases of the intestine that severely affect the quality of life of patients. The pathogenesis of this disease is caused by complex and interactive neural networks composed of factors such as genetic susceptibility, external environment, immune disorders, and intestinal barrier dysfunction. It is well known that there is a strong link between environmental stressors (also known as circadian clocks) that can influence circadian changes and inflammatory bowel disease. Among them, the biological clock is involved in the pathogenesis of inflammatory bowel disease by affecting the function of the intestinal barrier. Therefore, this review is aimed at systematically summarizing the latest research progress on the role of the circadian clock in the pathogenesis of inflammatory bowel disease by affecting intestinal barrier functions (intestinal mechanical barrier, intestinal immune barrier, intestinal microecological barrier, and intestinal chemical barrier) and the potential clinical value of clock genes in the management of inflammatory bowel disease, for the application of circadian clock therapy in the management of inflammatory bowel disease and then the benefit to the majority of patients.

show abstract

“…IELs represent one of the largest, non-organized lymphocyte population ( 58 ) and constitute one of the most abundant T cell populations of barrier immune cells ( 59 – 61 ). Furthermore, IELs with abundant cytoplasmic granules for cytotoxic activity and expression of effector cytokines [interferon-γ (IFN-γ), IL-2, IL-4, or IL-17] play a crucial role in limiting the dissemination of infectious pathogens and malignant cells and control of infiltration of epithelial surfaces by systemic cells ( 62 , 63 ). ILCs, identified in the recent years as an important subgroup of natural immune cells, have the dual characteristics of natural immune and acquired immune cells ( 64 ).…”

Section: Intestine Mucosal Immune Systemmentioning

confidence: 99%

The Functional Role of Lactoferrin in Intestine Mucosal Immune System and Inflammatory Bowel Disease

et al. 2021

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD), is one of the main types of intestinal inflammatory diseases with intestine mucosal immune disorder. Intestine mucosal immune system plays a remarkable and important role in the etiology and pathogenesis of IBD. Therefore, understanding the intestine mucosal immune mechanism is a key step to develop therapeutic interventions for IBD. Intestine mucosal immune system and IBD are influenced by various factors, such as inflammation, gut permeability, gut microbiota, and nutrients. Among these factors, emerging evidence show that nutrients play a key role in inflammation activation, integrity of intestinal barrier, and immune cell modulation. Lactoferrin (LF), an iron-binding glycoprotein belonging to transferrin family, is a dietary bioactive component abundantly found in mammalian milk. Notably, LF has been reported to perform diverse biological functions including antibacterial activity, anti-inflammatory activity, intestinal barrier protection, and immune cell modulation, and is involved in maintaining intestine mucosal immune homeostasis. The improved understanding of the properties of LF in intestine mucosal immune system and IBD will facilitate its application in nutrition, clinical medicine, and health. Herein, this review outlines the recent advancements on LF as a potential therapeutic intervention for IBD associated with intestine mucosal immune system dysfunction. We hope this review will provide a reference for future studies and lay a theoretical foundation for LF-based therapeutic interventions for IBD by understanding the particular effects of LF on intestine mucosal immune system.

show abstract

Intestinal intraepithelial lymphocytes: Maintainers of intestinal immune tolerance and regulators of intestinal immunity

Cited by 49 publications

References 96 publications

Enterovirus 71 Antagonizes Antiviral Effects of Type III Interferon and Evades the Clearance of Intestinal Intraepithelial Lymphocytes

Enterovirus 71 Antagonizes Antiviral Effects of Type III Interferon and Evades the Clearance of Intestinal Intraepithelial Lymphocytes

Biological Clock and Inflammatory Bowel Disease Review: From the Standpoint of the Intestinal Barrier

The Functional Role of Lactoferrin in Intestine Mucosal Immune System and Inflammatory Bowel Disease

Contact Info

Product

Resources

About