Fecal IgA Levels and Gut Microbiota Composition Are Regulated by Invariant Natural Killer T Cells

2019 ◽  
Vol 26 (5) ◽  
pp. 697-708 ◽  
Author(s):  
Cristhiane Favero de Aguiar ◽  
Angela Castoldi ◽  
Mariane T Amano ◽  
Aline Ignacio ◽  
Fernanda Fernandes Terra ◽  
...  
Keyword(s):  
T Cells ◽  
Gut Microbiota ◽  
Natural Killer ◽  
Natural Killer T Cells ◽  
Nkt Cells ◽  
Microbiota Composition ◽  
Inkt Cells ◽  
Intestinal Homeostasis ◽  
Killer T Cells ◽  
Gut Microbiota Composition

Abstract Background The gut microbiota is a key element to support host homeostasis and the development of the immune system. The relationship between the microbiota and immunity is a 2-way road, in which the microbiota contributes to the development/function of immune cells and immunity can affect the composition of microbes. In this context, natural killer T cells (NKT cells) are distinct T lymphocytes that play a role in gut immunity and are influenced by gut microbes. In our work, we investigated the involvement of invariant NKT cells (iNKT) in intestinal homeostasis. Results We found that iNKT-deficient mice (iNKT-KO) had reduced levels of fecal IgA and an altered composition of the gut microbiota, with increased Bacteroidetes. The absence of iNKT cells also affected TGF-β1 levels and plasma cells, which were significantly reduced in knockout (KO) mice. In addition, when submitted to dextran sodium sulfate colitis, iNKT-KO mice had worsening of colitis when compared with wild-type (WT) mice. To further address iNKT cell contribution to intestinal homeostasis, we adoptively transferred iNKT cells to KO mice, and they were submitted to colitis. Transfer of iNKT cells improved colitis and restored fecal IgA levels and gut microbiota. Conclusions Our results indicate that intestinal NKT cells are important modulators of intestinal homeostasis and that gut microbiota composition may be a potential target in the management of inflammatory bowel diseases.

scholarly journals Natural killer T cells play a necessary role in modulating of immune-mediated liver injury by gut microbiota

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Jianing Chen ◽  
Yingfeng Wei ◽  
Jianqin He ◽  
Guangying Cui ◽  
Yunan Zhu ◽  
...  
Keyword(s):  
T Cells ◽  
Liver Injury ◽  
Gut Microbiota ◽  
Natural Killer ◽  
Natural Killer T Cells ◽  
Immune Mediated ◽  
Killer T Cells ◽  
Natural Killer T

scholarly journals Expansion of invariant natural killer T cells from systemic lupus erythematosus patients by alpha-Galactosylceramide and IL-15

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261727
Author(s):  
Chien-Ya Hsu ◽  
Yu-Shan Chueh ◽  
Ming-Ling Kuo ◽  
Pei-Tzu Lee ◽  
Hsiu-Shan Hsiao ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Natural Killer ◽  
Lupus Erythematosus ◽  
Natural Killer T Cells ◽  
Inkt Cell ◽  
Inkt Cells ◽  
Systemic Lupus ◽  
Killer T Cells ◽  
Invariant Natural Killer

CD1d-restricted invariant natural killer T cells (iNKT cells) may play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Interleukin (IL)-15 is a pro-inflammatory cytokine which is over-expressed in SLE patients. In the present study, we investigated the iNKT cell expansion of mononuclear cells (MNCs) from SLE patients following 10 days’ culture with α-galactosylceramide (α-Galcer) and /or IL-15. We sought to determine the phenotypic and functional characteristics of the expanded iNKT cells compared to healthy controls and correlated with disease activity. We observed that 1. The percentages of Vα24+/Vβ11+ iNKT cells following 10-day incubation was lower in SLE groups compared to controls; 2. The percentages and absolute numbers of Vα24+/Vβ11+ iNKT cells were expanded by α-galactosylceramide (α-Galcer), and further enhanced with IL-15 in SLE patient, but the effect of IL-15 was much lower than controls; 3.IL-15 +α-Galcer expanded CD3+/CD56+ NKT-like cells from SLE patients, especially with active disease 4. The CD161+ Vα24+/Vβ11+ iNKT cells in SLE were more responsive to α-Galcer stimulation than the CD161- counterpart; 5. IL-15 decreased apoptosis of α-Galcer activated SLE iNKT cells; 6. IL-15 enhanced CD69, CD1d and CD11a expression on α-Galcer treated iNKT cells; 7. The IL-4 production of iNKT cells was decreased in SLE patients compared to controls; 8. IL-15 increased IFN-γ and IL-4 production of SLE iNKT cells; 8. IL-15 failed to augment the ability of iNKT cells to aid NK-mediated K562 cytolysis in SLE patients; 9. CD161 positivity, granzyme B and perforin expression of α-Galcer+IL-15 expanded iNKT cells correlated with C3 levels in SLE patients. Taken together, our results demonstrated numeric and functional deficiency of iNKT cells and their response to IL-15 in SLE patients. Our finding may provide insight for using adoptive iNKT cell therapy in autoimmune diseases.

scholarly journals Co-accumulation of Dendritic Cells and Natural Killer T Cells within Rupture-prone Regions in Human Atherosclerotic Plaques

2005 ◽  
Vol 53 (6) ◽  
pp. 781-785 ◽  
Author(s):  
Yuri V. Bobryshev ◽  
Reginald S.A. Lord
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Natural Killer ◽  
Natural Killer T Cells ◽  
Nkt Cells ◽  
Atherosclerotic Plaques ◽  
Lipid Antigens ◽  
Atherosclerotic Lesions ◽  
Killer T Cells ◽  
Natural Killer T

We previously reported that CD1d, a molecule responsible for the presentation of lipid antigens, is expressed in atherosclerotic lesions and that its expression is restricted to dendritic cells. Recent studies demonstrating that CD1d-restricted natural killer T (NKT) cells are involved in atherogenesis prompted the present study investigating whether NKT cells are present in human atherosclerotic lesions and, if so, whether there is an association between NKT cells and dendritic cells. We found that NKT cells do accumulate in rupture-prone shoulders of atherosclerotic plaques and observed direct contacts of dendritic cells with NKT cells in rupture-prone regions of plaque.

scholarly journals Third-party CD4+ invariant natural killer T cells protect from murine GVHD lethality

Blood ◽  
2015 ◽  
Vol 125 (22) ◽  
pp. 3491-3500 ◽  
Author(s):  
Dominik Schneidawind ◽  
Jeanette Baker ◽  
Antonio Pierini ◽  
Corina Buechele ◽  
Richard H. Luong ◽  
...  
Keyword(s):  
T Cells ◽  
Natural Killer ◽  
Natural Killer T Cells ◽  
Third Party ◽  
Low Doses ◽  
Inkt Cells ◽  
Key Points ◽  
Killer T Cells ◽  
Invariant Natural Killer ◽  
Natural Killer T

Key Points Low doses of adoptively transferred third-party CD4+ iNKT cells protect from lethal GVHD while preserving graft-versus-tumor effects. Third-party CD4+ iNKT cells are rejected early after transplantation yet protect from GVHD lethality through donor Tregs.

scholarly journals Type I natural killer T cells suppress tumors caused by p53 loss in mice

Blood ◽  
2009 ◽  
Vol 113 (25) ◽  
pp. 6382-6385 ◽  
Author(s):  
Jeremy B. Swann ◽  
Adam P. Uldrich ◽  
Serani van Dommelen ◽  
Janelle Sharkey ◽  
William K. Murray ◽  
...  
Keyword(s):  
T Cells ◽  
Natural Killer ◽  
Immune Surveillance ◽  
Tumor Development ◽  
Natural Killer T Cells ◽  
Nkt Cells ◽  
Type I ◽  
Killer T Cells ◽  
Natural Killer T

Abstract CD1d-restricted T cells are considered to play a host protective effect in tumor immunity, yet the evidence for a role of natural killer T (NKT) cells in tumor immune surveillance has been weak and data from several tumor models has suggested that some (type II) CD1d-restricted T cells may also suppress some types of antitumor immune response. To substantiate an important role for CD1d-restricted T cells in host response to cancer, we have evaluated tumor development in p53+/− mice lacking either type I NKT cells (TCR Jα18−/−) or all CD1d-restricted T cells (CD1d−/−). Our findings support a key role for type I NKT cells in suppressing the onset of sarcomas and hematopoietic cancers caused by p53 loss but do not suggest that other CD1d-restricted T cells are critical in regulating the same tumor development.

NK1.1− natural killer T cells upregulate interleukin-17 expression in experimental lupus nephritis

2021 ◽  
Vol 320 (5) ◽  
pp. F772-F788
Author(s):  
Jung Nam An ◽  
Seungwon Ryu ◽  
Yong Chul Kim ◽  
Kyung Don Yoo ◽  
Jangwook Lee ◽  
...  
Keyword(s):  
T Cells ◽  
Lupus Nephritis ◽  
Immune Responses ◽  
Natural Killer ◽  
Significant Contribution ◽  
Natural Killer T Cells ◽  
Nkt Cells ◽  
Interleukin 17 ◽  
Killer T Cells ◽  
Natural Killer T

This study makes a significant contribution to the literature because our results indicate that IL-17 is upregulated in lupus nephritis and that natural killer T (NKT) cells are involved in its pathogenesis. Activation of NKT cells regulates IL-17-related immune responses, both systemically and in the kidney, and this mainly involves NK1.1− NKT cells. Furthermore, IL-17-secreting NK1.1− NKT cells could serve as a diagnostic and therapeutic target for lupus nephritis.

scholarly journals Enhanced Gamma Interferon Production through Activation of Vα14+ Natural Killer T Cells by α-Galactosylceramide in Interleukin-18-Deficient Mice with Systemic Cryptococcosis

2001 ◽  
Vol 69 (11) ◽  
pp. 6643-6650 ◽  
Author(s):  
Kazuyoshi Kawakami ◽  
Yuki Kinjo ◽  
Satomi Yara ◽  
Kaori Uezu ◽  
Yoshinobu Koguchi ◽  
...  
Keyword(s):  
T Cells ◽  
Natural Killer ◽  
Natural Killer T Cells ◽  
Nkt Cells ◽  
Gamma Interferon ◽  
Interleukin 18 ◽  
Enhanced Production ◽  
Ifn Γ ◽  
Killer T Cells ◽  
Natural Killer T

ABSTRACT We showed recently that activation of Vα14+ natural killer T cells (NKT cells) by α-galactosylceramide (α-GalCer) resulted in increased gamma interferon (IFN-γ) production and host resistance to intravenous infection with Cryptococcus neoformans. In other studies, interleukin-18 (IL-18) activated NKT cells in collaboration with IL-12, suggesting the possible contribution of this cytokine to α-GalCer-induced IFN-γ synthesis. Here we examined the role of IL-18 in α-GalCer-induced Th1 response by using IL-18KO mice with this infection. In these mice, levels of IFN-γ in serum and its synthesis in vitro by spleen cells stimulated with live organisms were not reduced, but rather enhanced, compared to those in wild-type (WT) mice, while such production was completely absent in IL-12KO mice. The enhanced production of IFN-γ correlated with increased IL-12 synthesis but not with reduced production of IL-4, which was rather increased. IFN-γ synthesis in IL-18KO mice was abolished by neutralizing anti-IL-12 antibody and significantly inhibited by neutralization of endogenous IL-4 with a specific monoclonal antibody. In addition, administration of recombinant IL-4 significantly enhanced the production of IFN-γ in WT mice. Finally, the enhanced production of IFN-γ in IL-18KO mice correlated with increased host defense against cryptococcal infection, as indicated by enhancement in α-GalCer-related clearance of microorganisms. Our results indicated that in IL-18KO mice, IFN-γ synthesis was enhanced through overproduction of IL-12 and IL-4 after intravenous infection with C. neoformans and a ligand-specific activation of Vα14+ NKT cells.

scholarly journals CD4+ invariant natural killer T cells protect from murine GVHD lethality through expansion of donor CD4+CD25+FoxP3+ regulatory T cells

Blood ◽  
2014 ◽  
Vol 124 (22) ◽  
pp. 3320-3328 ◽  
Author(s):  
Dominik Schneidawind ◽  
Antonio Pierini ◽  
Maite Alvarez ◽  
Yuqiong Pan ◽  
Jeanette Baker ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Natural Killer ◽  
Natural Killer T Cells ◽  
Low Doses ◽  
Inkt Cells ◽  
Alloreactive T Cells ◽  
Key Points ◽  
Killer T Cells ◽  
Invariant Natural Killer

Key Points Low doses of adoptively transferred donor CD4+ iNKT cells protect from GVHD while preserving graft-versus-tumor effects. Donor CD4+ iNKT cells inhibit proliferation of alloreactive T cells and promote robust expansion of donor Tregs.

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