CD1d-Restricted Type II NKT Cells Reactive With Endogenous Hydrophobic Peptides

Nishioka, Yusuke; Masuda, Sakiko; Tomaru, Utano; Ishizu, Akihiro

doi:10.3389/fimmu.2018.00548

Cited by 31 publications

(29 citation statements)

References 61 publications

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“…They are important mediators of immune responses and were suggested as potential targets for immunotherapy (5). In response to a wide range of antigens, these cells are rapidly activated and exhibit both pro-inflammatory and immunoregulatory characteristics, resulting in harmful or protective roles in infections, autoimmune diseases, allergies, and cancer (6).…”

Section: Nkt Cells Are a Unique Subset Of Regulatory Lymphocytesmentioning

confidence: 99%

β-Glycosphingolipids as Mediators of Both Inflammation and Immune Tolerance: A Manifestation of Randomness in Biological Systems

Ilan

2019

Front. Immunol.

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Plasticity in biological systems is attributed to the combination of multiple parameters which determine function. These include genotypic, phenotypic, and environmental factors. While biological processes can be viewed as ordered and sequential, biological randomness was suggested to underline part of them. The present review looks into the concept of randomness in biological systems by exploring the glycosphingolipids-NKT cells example. NKT cells are a unique subset of regulatory lymphocytes which play a role in both inflammation and tolerance. Glycosphingolipids promote an immune balance by changing different arms of the immune system in opposing environments. Traditional immunology looks at skewing the immune system into different directions by different types of activation of the same cell stimulation of different cells subsets, use of different ligands, or different the effect of different immune environments. While these may explain some of the effects, the lack of consistency and opposing results under similar settings may involve randomness which may also be part of real life effects of immunomodulatory agents. It means that several of the biological processes, cannot be explained by simple linear models, and may involve more complex concepts. The application for these concepts for improving therapies to patients with Gaucher disease are discussed. SUMMARY The use of different ligands that target a variety of cell subsets in different immune environments may underlie differences in the functionality of NKT cells and their variability in response to NKT-based therapies. The novel concept of randomness in biology means that several biological processes cannot be solely explained by simple linear models and may instead involve much more complicated schemes of random disorder. These may have implications on future design of therapeutic regimens for improving the response to current treatments.

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Section: Nkt Cells Are a Unique Subset Of Regulatory Lymphocytesmentioning

confidence: 99%

β-Glycosphingolipids as Mediators of Both Inflammation and Immune Tolerance: A Manifestation of Randomness in Biological Systems

Ilan

2019

Front. Immunol.

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“…In contrast, type II NKT cells are not reactive to αGalCer, are more abundant than iNKT cells in humans and consist of CD1d-restricted T cells that express a diverse TCR repertoire but not the semi invariant TCR α-chain expressed by iNKT cells ( 12 ). Type II NKT cells can also recognize a variety of lipids antigens, including microbial and endogenous glycolipids and phospholipids as well as endogenous hydrophobic peptides ( 21 ). Usually, in comparison to the αGalCer/CD1d/TCR interactions, lipid antigens recognized by type II NKT cells, for example, sulfatides or lysophosphatidylcholine (LPC), binds with lower affinity to CD1d molecules and, accordingly, form relatively less stable tetrameric complexes ( 22 – 24 ), whereas αGalCer-loaded CD1d tetramers form stable complexes ( 25 , 26 ).…”

Section: Inkt and Type II Nkt Cell Subsetsmentioning

confidence: 99%

Complex Network of NKT Cell Subsets Controls Immune Homeostasis in Liver and Gut

et al. 2018

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The liver-gut immune axis is enriched in several innate immune cells, including innate-like unconventional and adaptive T cells that are thought to be involved in the maintenance of tolerance to gut-derived antigens and, at the same time, enable effective immunity against microbes. Two subsets of lipid-reactive CD1d-restricted natural killer T (NKT) cells, invariant NKT (iNKT) and type II NKT cells present in both mice and humans. NKT cells play an important role in regulation of inflammation in the liver and gut due to their innate-like properties of rapid secretion of a myriad of pro-inflammatory and anti-inflammatory cytokines and their ability to influence other innate cells as well as adaptive T and B cells. Notably, a bi-directional interactive network between NKT cells and gut commensal microbiota plays a crucial role in this process. Here, we briefly review recent studies related to the cross-regulation of both NKT cell subsets and how their interactions with other immune cells and parenchymal cells, including hepatocytes and enterocytes, control inflammatory diseases in the liver, such as alcoholic and non-alcoholic steatohepatitis, as well as inflammation in the gut. Overwhelming experimental data suggest that while iNKT cells are pathogenic, type II NKT cells are protective in the liver. Since CD1d-dependent pathways are highly conserved from mice to humans, a detailed cellular and molecular understanding of these immune regulatory pathways will have major implications for the development of novel therapeutics against inflammatory diseases of liver and gut.

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“…Compared to iNKT cells, type II NKT cells express relatively diverse TCRs that can recognize antigens derived from microbial, endogenous glycolipids, phospholipids and endogenous hydrophobic peptides presented by CD1d molecules ( 33 ). Type II NKT cells are unable to recognize α-linked glycolipids, for example, α-Galcer, but are responded to β-linked glycolipids ( 34 ).…”

Section: The Biology Of Innate T Cellsmentioning

confidence: 99%

The Role of CD1d and MR1 Restricted T Cells in the Liver

Huang

Shi

et al. 2018

Front. Immunol.

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The liver is one of the most important immunological organs that remains tolerogenic in homeostasis yet promotes rapid responses to pathogens in the presence of a systemic infection. The composition of leucocytes in the liver is highly distinct from that of the blood and other lymphoid organs, particularly with respect to enrichment of innate T cells, i.e., invariant NKT cells (iNKT cells) and Mucosal-Associated Invariant T cells (MAIT cells). In recent years, studies have revealed insights into their biology and potential roles in maintaining the immune-environment in the liver. As the primary liver-resident immune cells, they are emerging as significant players in the human immune system and are associated with an increasing number of clinical diseases. As such, innate T cells are promising targets for modifying host defense and inflammation of various liver diseases, including viral, autoimmune, and those of tumor origin. In this review, we emphasize and discuss some of the recent discoveries and advances in the biology of innate T cells, their recruitment and diversity in the liver, and their role in various liver diseases, postulating on their potential application in immunotherapy.

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CD1d-Restricted Type II NKT Cells Reactive With Endogenous Hydrophobic Peptides

Cited by 31 publications

References 61 publications

β-Glycosphingolipids as Mediators of Both Inflammation and Immune Tolerance: A Manifestation of Randomness in Biological Systems

β-Glycosphingolipids as Mediators of Both Inflammation and Immune Tolerance: A Manifestation of Randomness in Biological Systems

Complex Network of NKT Cell Subsets Controls Immune Homeostasis in Liver and Gut

The Role of CD1d and MR1 Restricted T Cells in the Liver

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