scholarly journals Linking CD11b+Dendritic Cells and Natural Killer T Cells to Plaque Inflammation in Atherosclerosis

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Miche Rombouts ◽  
Rachid Ammi ◽  
Ilse Van Brussel ◽  
Lynn Roth ◽  
Benedicte Y. De Winter ◽  
...  
Keyword(s):  
Natural Killer ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Atherosclerotic Lesion ◽  
Nkt Cells ◽  
Western Society ◽  
Markers Of Inflammation ◽  
Inflammatory Status ◽  
Plaque Inflammation ◽  
Natural Killer T

Atherosclerosis remains the leading cause of death and disability in our Western society. To investigate whether the dynamics of leukocyte (sub)populations could be predictive for plaque inflammation during atherosclerosis, we analyzed innate and adaptive immune cell distributions in blood, plaques, and lymphoid tissue reservoirs in apolipoprotein E-deficient (ApoE−/−) mice and in blood and plaques from patients undergoing endarterectomy. Firstly, there was predominance of the CD11b+conventional dendritic cell (cDC) subset in the plaque. Secondly, a strong inverse correlation was observed between CD11b+cDC or natural killer T (NKT) cells in blood and markers of inflammation in the plaque (including CD3, T-bet, CCR5, and CCR7). This indicates that circulating CD11b+cDC and NKT cells show great potential to reflect the inflammatory status in the atherosclerotic plaque. Our results suggest that distinct changes in inflammatory cell dynamics may carry biomarker potential reflecting atherosclerotic lesion progression. This not only is crucial for a better understanding of the immunopathogenesis but also bares therapeutic potential, since immune cell-based therapies are emerging as a promising novel strategy in the battle against atherosclerosis and its associated comorbidities. The cDC-NKT cell interaction in atherosclerosis serves as a good candidate for future investigations.

scholarly journals Targeting Natural Killer T Cells in Solid Malignancies

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1329
Author(s):  
Zewde Ingram ◽  
Shriya Madan ◽  
Jenoy Merchant ◽  
Zakiya Carter ◽  
Zen Gordon ◽  
...  
Keyword(s):  
T Cells ◽  
Natural Killer ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Cell Subset ◽  
Adaptive Immune System ◽  
Nkt Cells ◽  
Class I Mhc ◽  
Effector Functions ◽  
Natural Killer T

Natural killer T (NKT) cells are a unique subset of lymphocytes that recognize lipid antigens in the context of the non-classical class I MHC molecule, CD1d, and serve as a link between the innate and adaptive immune system through their expeditious release of cytokines. Whereas NKT have well-established roles in mitigating a number of human diseases, herein, we focus on their role in cancer. NKT cells have been shown to directly and indirectly mediate anti-tumor immunity and manipulating their effector functions can have therapeutic significances in treatment of cancer. In this review, we highlight several therapeutic strategies that have been used to harness the effector functions of NKT cells to target different types of solid tumors. We also discuss several barriers to the successful utilization of NKT cells and summarize effective strategies being developed to harness the unique strengths of this potent population of T cells. Collectively, studies investigating the therapeutic potential of NKT cells serve not only to advance our understanding of this powerful immune cell subset, but also pave the way for future treatments focused on the modulation of NKT cell responses to enhance cancer immunotherapy.

Participatory role of natural killer and natural killer T cells in atherosclerosis: lessons learned from in vivo mouse studiesThis paper is one of a selection of papers published in this Special Issue, entitled Young Investigator's Forum.

2006 ◽  
Vol 84 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Stewart C. Whitman ◽  
Tanya A. Ramsamy
Keyword(s):  
Natural Killer ◽  
Complex Disease ◽  
Immune Cell ◽  
Disease Process ◽  
Density Lipoprotein ◽  
Nkt Cells ◽  
Lessons Learned ◽  
Natural Killer T

Atherosclerosis is a multifactor, highly complex disease with numerous aetiologies that work synergistically to promote lesion development. One of the emerging components that drive the development of both early- and late-stage atherosclerotic lesions is the participation of both the innate and acquired immune systems. In both humans and animal models of atherosclerosis, the most prominent cells that infiltrate evolving lesions are macrophages and T lymphocytes. The functional loss of either of these cell types reduces the extent of atherosclerosis in mice that were rendered susceptible to the disease by deficiency of either apolipoprotein E or the LDL (low density lipoprotein) receptor. In addition to these major immune cell participants, a number of less prominent leukocyte populations that can modulate the atherogenic process are also involved. This review will focus on the participatory role of two “less prominent” immune components, namely natural killer (NK) cells and natural killer T (NKT) cells. Although this review will highlight the fact that both NK and NKT cells are not sufficient for causing the disease, the roles played by both these cells types are becoming increasingly important in understanding the complexity of this disease process.

scholarly journals Invariant Natural Killer T-Cells and Total CD1d Restricted Cells Differentially Influence Lipid Metabolism and Atherosclerosis in Low Density Receptor Deficient Mice

2019 ◽  
Vol 20 (18) ◽  
pp. 4566
Author(s):  
Paul A. VanderLaan ◽  
Catherine A. Reardon ◽  
Veneracion G. Cabana ◽  
Chyung-Ru Wang ◽  
Godfrey S. Getz
Keyword(s):  
Lipid Metabolism ◽  
Natural Killer ◽  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Atherosclerotic Lesion ◽  
Nkt Cells ◽  
Type I ◽  
Type Ii ◽  
Inkt Cells ◽  
Natural Killer T

Natural killer T (NKT) cells are a distinct subset of lymphocytes that bridge the innate and adaptive immune response and can be divided into type I invariant NKT cells (iNKT) and type II NKT cells. The objective of this study is to examine the effects of NKT cell on lipid metabolism and the initiation and progression of atherosclerosis in LDL receptor deficient (LDLR−/−) mice. Mice were fed an atherogenic diet for 4 or 8 weeks and plasma lipids, lipoproteins, and atherosclerosis were measured. The selective absence of iNKT cells in Jα18−/−LDLR−/− mice led to an increase in plasma cholesterol levels in female mice. Transgenic Vα14tg/LDLR−/− mice with elevated numbers of iNKT cells had increased late atherosclerosis of the innominate artery, though absence of either iNKT cells or all NKT cells and other CD1d expressing cells had varying effects on atherosclerotic lesion burden in the ascending aortic arch and aortic root. These studies not only highlight the potential modulatory role played by NKT cells in atherosclerosis and lipid metabolism, but also raise the possibility that divergent roles may be played by iNKT and CD1d restricted cells such as type II NKT cells or other CD1d expressing cells.

86: Activation of Natural Killer T (NKT) Cells by Alpha-Galactosylceramide Mediates Clearance of E. Coli in Murine Urinary Tract Infection

2004 ◽  
Vol 171 (4S) ◽  
pp. 22-23
Author(s):  
Shingo Minagawa ◽  
Chikara Ohyama ◽  
Shingo Hatakeyama ◽  
Kazunari Sato ◽  
Shigeru Sato ◽  
...  
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Natural Killer ◽  
Nkt Cells ◽  
E Coli ◽  
Natural Killer T

scholarly journals Mechanisms imposing the Vβ bias of Vα14 natural killer T cells and consequences for microbial glycolipid recognition

2006 ◽  
Vol 203 (5) ◽  
pp. 1197-1207 ◽  
Author(s):  
Datsen G. Wei ◽  
Shane A. Curran ◽  
Paul B. Savage ◽  
Luc Teyton ◽  
Albert Bendelac
Keyword(s):  
T Cells ◽  
Natural Killer ◽  
Optimal Solution ◽  
Nkt Cells ◽  
Cell Repertoire ◽  
Transgenic Cells ◽  
Α Chain ◽  
Natural Killer T

Mouse and human natural killer T (NKT) cells recognize a restricted set of glycosphingolipids presented by CD1d molecules, including self iGb3 and microbial α-glycuronosylceramides. The importance of the canonical Vα14-Jα18 TCR α chain for antigen recognition by NKT cells is well recognized, but the mechanisms underlying the Vβ8, Vβ7, and Vβ2 bias in mouse have not been explored. To study the influences of thymic selection and the constraints of pairing with Vα14-Jα18, we have created a population of mature T cells expressing Vα14-Jα18 TCR α chain in CD1d-deficient mice and studied its recognition properties in vitro and in vivo. Transgenic cells expressed a diverse Vβ repertoire but their recognition of endogenous ligands and synthetic iGb3 was restricted to the same biased Vβ repertoire as expressed in natural NKT cells. In contrast, α-GalCer, a synthetic homologue of microbial α-glycuronosylceramides, was recognized by a broader set of Vβ chains, including the biased NKT set but also Vβ6, Vβ9, Vβ10, and Vβ14. These surprising findings demonstrate that, whereas Vβ8, Vβ7, and Vβ2 represent the optimal solution for recognition of endogenous ligand, many Vβ chains that are potentially useful for the recognition of foreign lipids fail to be selected in the NKT cell repertoire.

scholarly journals Chewing the fat on natural killer T cell development

2006 ◽  
Vol 203 (10) ◽  
pp. 2229-2232 ◽  
Author(s):  
Dale I. Godfrey ◽  
Malcolm J. McConville ◽  
Daniel G. Pellicci
Keyword(s):  
Natural Killer ◽  
Lysosomal Storage Diseases ◽  
Nkt Cells ◽  
Cell Development ◽  
Lysosomal Storage ◽  
Nkt Cell ◽  
Diverse Range ◽  
Natural Killer T Cell ◽  
New Evidence ◽  
Natural Killer T

Natural killer T cells (NKT cells) are selected in the thymus by self-glycolipid antigens presented by CD1d molecules. It is currently thought that one specific component of the lysosomal processing pathway, which leads to the production of isoglobotrihexosylceramide (iGb3), is essential for normal NKT cell development. New evidence now shows that NKT cell development can be disrupted by a diverse range of mutations that interfere with different elements of the lysosomal processing and degradation of glycolipids. This suggests that lysosomal storage diseases (LSDs) in general, rather than one specific defect, can disrupt CD1d antigen presentation, leading to impaired development of NKT cells.

Abstract 039: Natural Killer T Cells Play Protective Roles in Cardiovirus-Induced Myocarditis by Inducing Anti-Viral and Regulatory Cytokines

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Fumitaka Sato ◽  
Seiichi Omura ◽  
Nicholas E Martinez ◽  
Eiichiro Kawai ◽  
Sadie F Pearson ◽  
...  
Keyword(s):  
Natural Killer ◽  
Acute Phase ◽  
Viral Myocarditis ◽  
Chronic Phase ◽  
Nkt Cells ◽  
Viral Clearance ◽  
Left Ventricular Ejection ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Natural Killer T

Picornavirus infections have been known as a leading cause of viral myocarditis in humans. Theiler’s murine encephalomyelitis virus (TMEV) belongs to the genus Cardiovirus, the family Picornaviridae, and can cause myocarditis in susceptible mice. In viral myocarditis, viral replication in the heart and/or immune responses against virus as well as cardiac antigens (autoimmunity) can contribute to the pathogenesis. Natural killer T (NKT) cells can play a regulatory role in viral infections by producing anti-viral and anti-inflammatory cytokines; interferon (IFN)-γ can contribute to either viral clearance or tissue damage (immunopathology), while anti-inflammatory interleukin (IL)-10 has been suggested to regulate viral clearance or immunopathology. To determine the role of NKT cells in TMEV-induced myocarditis, we infected wild-type (WT) and NKT knockout (NKT KO, Jα18 KO) mice with TMEV. Myocarditis was monitored by echocardiography using the Vevo 770 system. During the acute (day 7) or chronic phase (day 60) of TMEV infection, cardiac pathology was evaluated by hematoxylin and eosin staining, and production of cytokines, including IFN-γ and IL-10, from spleen cells was measured by enzyme-linked immunosorbent assays. During the acute phase, the levels of left ventricular ejection fraction were significantly lower in NKT KO mice than in WT mice. Immunologically, NKT KO mice had lower levels of IFN-γ production than WT mice [IFN-γ (pg/ml): WT, 768 ± 533; NKT KO, 293 ± 190]. During the chronic phase, high intensity cardiac lesions were observed by echocardiography in NKT KO mice, but not in WT mice. Histologically, NKT KO mice developed moderate inflammation with basophilic degeneration and calcification in the heart, while WT mice had only mild inflammation in the heart. Immunologically, NKT KO mice had lower levels of IL-10 production compared with WT mice [IL-10 (pg/ml): WT, 1771 ± 381; NKT KO, 1199 ± 160]. These results suggest that NKT cells play a protective role in viral myocarditis by producing IFN-γ and IL-10, which contribute to viral clearance during the acute phase and the suppression of immunopathology during the chronic phase of disease, respectively.

scholarly journals Type I Natural Killer T Cells as Key Regulators of the Immune Response to Infectious Diseases

2020 ◽  
Vol 34 (2) ◽  
pp. e00232-20
Author(s):  
Nicolás M. S. Gálvez ◽  
Karen Bohmwald ◽  
Gaspar A. Pacheco ◽  
Catalina A. Andrade ◽  
Leandro J. Carreño ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Infectious Diseases ◽  
Natural Killer ◽  
Nkt Cells ◽  
Interleukin 4 ◽  
Type I ◽  
Inkt Cells ◽  
Class I Mhc ◽  
Natural Killer T

SUMMARYThe immune system must work in an orchestrated way to achieve an optimal response upon detection of antigens. The cells comprising the immune response are traditionally divided into two major subsets, innate and adaptive, with particular characteristics for each type. Type I natural killer T (iNKT) cells are defined as innate-like T cells sharing features with both traditional adaptive and innate cells, such as the expression of an invariant T cell receptor (TCR) and several NK receptors. The invariant TCR in iNKT cells interacts with CD1d, a major histocompatibility complex class I (MHC-I)-like molecule. CD1d can bind and present antigens of lipid nature and induce the activation of iNKT cells, leading to the secretion of various cytokines, such as gamma interferon (IFN-γ) and interleukin 4 (IL-4). These cytokines will aid in the activation of other immune cells following stimulation of iNKT cells. Several molecules with the capacity to bind to CD1d have been discovered, including α-galactosylceramide. Likewise, several molecules have been synthesized that are capable of polarizing iNKT cells into different profiles, either pro- or anti-inflammatory. This versatility allows NKT cells to either aid or impair the clearance of pathogens or to even control or increase the symptoms associated with pathogenic infections. Such diverse contributions of NKT cells to infectious diseases are supported by several publications showing either a beneficial or detrimental role of these cells during diseases. In this article, we discuss current data relative to iNKT cells and their features, with an emphasis on their driving role in diseases produced by pathogenic agents in an organ-oriented fashion.

scholarly journals Natural killer T (NKT) cells accelerate Shiga toxin type 2 (Stx2) pathology in mice

2015 ◽  
Vol 6 ◽  
Author(s):  
Fumiko Obata ◽  
Priyanka B. Subrahmanyam ◽  
Aimee E. Vozenilek ◽  
Lauren M. Hippler ◽  
Tynae Jeffers ◽  
...  
Keyword(s):  
Natural Killer ◽  
Shiga Toxin ◽  
Nkt Cells ◽  
Natural Killer T

scholarly journals Natural Killer Dendritic Cells Enhance Immune Responses Elicited byα-Galactosylceramide-Stimulated Natural Killer T Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Sung Won Lee ◽  
Hyun Jung Park ◽  
Nayoung Kim ◽  
Seokmann Hong
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Natural Killer ◽  
Immune Cells ◽  
Tumor Antigens ◽  
Nkt Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Natural Killer T

Natural killer dendritic cells (NKDCs) possess potent anti-tumor activity, but the cellular effect of NKDC interactions with other innate immune cells is unclear. In this study, we demonstrate that the interaction of NKDCs and natural killer T (NKT) cells is required for the anti-tumor immune responses that are elicited byα-galactosylceramide (α-GC) in mice. The rapid and strong expression of interferon-γby NKDCs afterα-GC stimulation was dependent on NKT cells. Various NK and DC molecular markers and cytotoxic molecules were up-regulated followingα-GC administration. This up-regulation could improve NKDC presentation of tumor antigens and increase cytotoxicity against tumor cells. NKDCs were required for the stimulation of DCs, NK cells, and NKT cells. The strong anti-tumor immune responses elicited byα-GC may be due to the down-regulation of regulatory T cells. Furthermore, the depletion of NKDCs dampened the tumor clearance mediated byα-GC-stimulated NKT cellsin vivo. Taken together, these results indicate that complex interactions of innate immune cells might be required to achieve optimal anti-tumor immune responses during the early stages of tumorigenesis.

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