scholarly journals Infections, Reactions of Natural Killer T Cells and Natural Killer Cells, and Kidney Injury

2022 ◽  
Vol 23 (1) ◽  
pp. 479
Author(s):  
Takahiro Uchida ◽  
Shuhji Seki ◽  
Takashi Oda
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Fas Ligand ◽  
Cell Injury ◽  
Vascular Endothelial Cell ◽  
Kidney Injury ◽  
Nkt Cells ◽  
Renal Diseases ◽  
Natural Killer T

Natural killer T (NKT) cells and NK cells are representative innate immune cells that perform antitumor and antimicrobial functions. The involvement of these cells in various renal diseases, including acute kidney injury (AKI), has recently become evident. Murine NKT cells are activated and cause AKI in response to various stimuli, such as their specific ligand, cytokines, and bacterial components. Both renal vascular endothelial cell injury (via the perforin-mediated pathway) and tubular epithelial cell injury (via the tumor necrosis factor-alpha/Fas ligand pathway) are independently involved in the pathogenesis of AKI. NK cells complement the functions of NKT cells, thereby contributing to the development of infection-associated AKI. Human CD56+ T cells, which are a functional counterpart of murine NKT cells, as well as a subpopulation of CD56+ NK cells, strongly damage intrinsic renal cells in vitro upon their activation, possibly through mechanisms similar to those in mice. These cells are also thought to be involved in the acute exacerbation of pre-existing glomerulonephritis triggered by infection in humans, and their roles in sepsis-associated AKI are currently under investigation. In this review, we will provide an overview of the recent advances in the understanding of the association among infections, NKT and NK cells, and kidney injury, which is much more profound than previously considered. The important role of liver macrophages in the activation of NKT cells will also be introduced.

scholarly journals Roles of Natural Killer T Cells and Natural Killer Cells in Kidney Injury

2019 ◽  
Vol 20 (10) ◽  
pp. 2487 ◽  
Author(s):  
Takahiro Uchida ◽  
Seigo Ito ◽  
Hiroo Kumagai ◽  
Takashi Oda ◽  
Hiroyuki Nakashima ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Fas Ligand ◽  
Vascular Endothelial Cells ◽  
Kidney Injury ◽  
Nkt Cells ◽  
Renal Diseases ◽  
Renal Cells ◽  
Natural Killer T

Mouse natural killer T (NKT) cells and natural killer (NK) cells are innate immune cells that are highly abundant in the liver. In addition to their already-known antitumor and antimicrobial functions, their pathophysiological roles in the kidney have recently become evident. Under normal circumstances, the proportion of activated NKT cells in the kidney increases with age. Administration of a synthetic sphingoglycolipid ligand (alpha-galactosylceramide) further activates NKT cells, resulting in injury to renal vascular endothelial cells via the perforin-mediated pathway and tubular epithelial cells via the TNF-α/Fas ligand pathway, causing acute kidney injury (AKI) with hematuria. Activation of NKT cells by common bacterial DNA (CpG-ODN) also causes AKI. In addition, NKT cells together with B cells play significant roles in experimental lupus nephritis in NZB/NZW F1 mice through their Th2 immune responses. Mouse NK cells are also assumed to be involved in various renal diseases, and there may be complementary roles shared between NKT and NK cells. Human CD56+ T cells, a functional counterpart of mouse NKT cells, also damage renal cells through a mechanism similar to that of mice. A subpopulation of human CD56+ NK cells also exert strong cytotoxicity against renal cells and contribute to the progression of renal fibrosis.

scholarly journals Transcriptome and Function of Novel Immunosuppressive Autoreactive Invariant Natural Killer T Cells That Are Absent in Progressive Multiple Sclerosis

2021 ◽  
Vol 8 (6) ◽  
pp. e1065
Author(s):  
Belinda Carrión ◽  
Yawei Liu ◽  
Mahdieh Hadi ◽  
Jon Lundstrom ◽  
Jeppe Romme Christensen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Natural Killer ◽  
Protein Level ◽  
Fas Ligand ◽  
Nkt Cells ◽  
Tnf Receptor ◽  
Inkt Cells ◽  
Invariant Natural Killer ◽  
Natural Killer T

Background and ObjectiveThe aim of this study was to determine whether natural killer T (NKT) cells, including invariant (i) NKT cells, have clinical value in preventing the progression of multiple sclerosis (MS) by examining the mechanisms by which a distinct self-peptide induces a novel, protective invariant natural killer T cell (iNKT cell) subset.MethodsWe performed a transcriptomic and functional analysis of iNKT cells that were reactive to a human collagen type II self-peptide, hCII707-721, measuring differentially induced genes, cytokines, and suppressive capacity.ResultsWe report the first transcriptomic profile of human conventional vs novel hCII707-721–reactive iNKT cells. We determined that hCII707-721 induces protective iNKT cells that are found in the blood of healthy individuals but not progressive patients with MS (PMS). By transcriptomic analysis, we observed that hCII707-721 promotes their development and proliferation, favoring the splicing of full-length AKT serine/threonine kinase 1 (AKT1) and effector function of this unique lineage by upregulating tumor necrosis factor (TNF)-related genes. Furthermore, hCII707-721–reactive iNKT cells did not upregulate interferon (IFN)-γ, interleukin (IL)-4, IL-10, IL-13, or IL-17 by RNA-seq or at the protein level, unlike the response to the glycolipid alpha-galactosylceramide. hCII707-721–reactive iNKT cells increased TNFα only at the protein level and suppressed autologous-activated T cells through FAS-FAS ligand (FAS-FASL) and TNFα-TNF receptor I signaling but not TNF receptor II.DiscussionBased on their immunomodulatory properties, NKT cells have a potential value in the treatment of autoimmune diseases, such as MS. These significant findings suggest that endogenous peptide ligands can be used to expand iNKT cells, without causing a cytokine storm, constituting a potential immunotherapy for autoimmune conditions, including PMS.

scholarly journals Activated natural killer T cells in mice induce acute kidney injury with hematuria through possibly common mechanisms shared by human CD56+ T cells

2018 ◽  
Vol 315 (3) ◽  
pp. F618-F627 ◽  
Author(s):  
Takahiro Uchida ◽  
Hiroyuki Nakashima ◽  
Seigo Ito ◽  
Takuya Ishikiriyama ◽  
Masahiro Nakashima ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
T Cells ◽  
Endothelial Cells ◽  
Epithelial Cells ◽  
Natural Killer ◽  
Kidney Injury ◽  
Nkt Cells ◽  
Dependent Manner ◽  
Tubular Epithelial Cells ◽  
Natural Killer T

Although activation of mouse natural killer T (NKT) cells by α-galactosylceramide (α-GalCer) causes failure of multiple organs, including the kidneys, the precise mechanisms underlying kidney injury remain unclear. Here, we showed that α-GalCer-activated mouse NKT cells injured both kidney vascular endothelial cells and tubular epithelial cells in vitro, causing acute kidney injury (AKI) with hematuria in middle-aged mice. The perforin-mediated pathway was mainly involved in glomerular endothelial cell injury, whereas the TNF-α/Fas ligand pathway played an important role in the injury of tubular epithelial cells. Kidney injury in young mice was mild but could be significantly exacerbated if NKT cells were strongly activated by NK cell depletion alone or in combination with IL-12 pretreatment. When stimulated by a combination of IL-2 and IL-12, human CD56+ T cells, a functional counterpart of mouse NKT cells, also damaged both glomerular endothelial cells and tubular epithelial cells, with the former being affected in a perforin-dependent manner. These data suggest that both mouse NKT cells and human CD56+ T cells are integral to the processes that mediate AKI. Targeting CD56+ T cells may, therefore, be a promising approach to treat AKI.

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 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 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.

scholarly journals Low doses of natural killer T cells provide protection from acute graft-versus-host disease via an IL-4–dependent mechanism

Blood ◽  
2011 ◽  
Vol 117 (11) ◽  
pp. 3220-3229 ◽  
Author(s):  
Dennis B. Leveson-Gower ◽  
Janelle A. Olson ◽  
Emanuela I. Sega ◽  
Richard H. Luong ◽  
Jeanette Baker ◽  
...  
Keyword(s):  
T Cells ◽  
Natural Killer ◽  
Graft Versus Host Disease ◽  
B Cell Lymphoma ◽  
Nkt Cells ◽  
Host Disease ◽  
Graft Versus Host ◽  
Gastrointestinal Pathology ◽  
Dependent Mechanism ◽  
Natural Killer T

Abstract CD4+ natural killer T (NKT) cells, along with CD4+CD25+ regulatory T cells (Tregs), are capable of controlling aberrant immune reactions. We explored the adoptive transfer of highly purified (> 95%) CD4+NKT cells in a murine model of allogeneic hematopoietic cell transplantation (HCT). NKT cells follow a migration and proliferation pattern similar to that of conventional T cells (Tcons), migrating initially to secondary lymphoid organs followed by infiltration of graft-versus-host disease (GVHD) target tissues. NKT cells persist for more than 100 days and do not cause significant morbidity or mortality. Doses of NKT cells as low as 1.0 × 104 cells suppress GVHD caused by 5.0 × 105 Tcons in an interleukin-4 (IL-4)–dependent mechanism. Protective doses of NKT cells minimally affect Tcon proliferation, but cause significant reductions in interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) production by donor Tcons and in skin, spleen, and gastrointestinal pathology. In addition, NKT cells do not impact the graft-versus-tumor (GVT) effect of Tcons against B-cell lymphoma-1 (BCL-1) tumors. These studies elucidate the biologic function of donor-type CD4+NKT cells in suppressing GVHD in an allogeneic transplantation setting, demonstrating clinical potential in reducing GVHD in HCT.

scholarly journals Natural Killer T Cells in Various Mouse Models of Hepatitis

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Jun Guan ◽  
Gang Wang ◽  
Qin Yang ◽  
Chao Chen ◽  
Jingwen Deng ◽  
...  
Keyword(s):  
Natural Killer ◽  
Mouse Models ◽  
Fas Ligand ◽  
Basic Research ◽  
Neutrophil Infiltration ◽  
Nkt Cells ◽  
Liver Injuries ◽  
Integral Role ◽  
Natural Killer T

Natural killer T (NKT) cells are a key component of innate immunity. Importantly, a growing body of evidence indicates that NKT cells play an integral role in various acute and chronic liver injuries. NKT cells participate in the progression of an injury through the secretion of cytokines, which promote neutrophil infiltration and enhance Fas ligand (FasL) and granzyme-mediated NKT cytotoxic activity. Therefore, examining the role of NKT cells in hepatic disease is critical for a comprehensive understanding of disease pathogenesis and may provide insight into novel approaches for treatment. For more than a century, mouse models that imitate the physiopathological conditions of human disease have served as a critical tool in biological and medical basic research, including studies of liver disease. Here, we review the role of NKT cells in various mouse models of hepatitis.

scholarly journals Natural killer T cells in lipoprotein metabolism and atherosclerosis

2011 ◽  
Vol 106 (11) ◽  
pp. 814-819 ◽  
Author(s):  
Godfrey Getz ◽  
Paul VanderLaan ◽  
Catherine Reardon
Keyword(s):  
T Cells ◽  
T Cell ◽  
Natural Killer ◽  
Cell Receptor ◽  
Nkt Cells ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Invariant Nkt Cells ◽  
Adaptive Immune ◽  
Natural Killer T

SummaryCells of both the innate and adaptive immune system participate in the development of atherosclerosis, a chronic inflammatory disorder of medium and large arteries. Natural killer T (NKT) cells express surface markers characteristic of natural killer cells and conventional T cells and bridge the innate and adaptive immune systems. The development and activation of NKT cells is dependent upon CD1d, a MHC-class I-type molecule that presents lipids, especially glycolipids to the T cell receptors on NKT cells. There are two classes of NKT cells; invariant NKT cells that express a semi-invariant T cell receptor and variant NKT cells. This review summarises studies in murine models in which the effect of the activation, overexpression or deletion of NKT cells or only invariant NKT cells on atherosclerosis has been examined.

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