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https://www.readbyqxmd.com/read/28104122/role-of-natural-killer-cells-in-the-innate-immune-system-after-intraportal-islet-transplantation-in-mice
#1
Y Saeki, K Ishiyama, N Ishida, Y Tanaka, H Ohdan
BACKGROUND: Both liver natural killer (NK) and NK T cells of the innate immune system play a crucial role in islet graft loss after intraportal islet transplantation, although a relationship between NK and NK T cells in islet loss has not been proven. In this study, we investigated the role of NK cells in the innate immune system in islet graft loss after intraportal islet transplantation. METHODS: To investigate the involvement of liver NK cells in islet destruction, we assessed the differences in graft survival after intraportal islet transplantation between CD1d(-/-) diabetic mice and NK cell-depleted CD1d(-/-) diabetic mice...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28095739/expression-and-localization-of-fibroblast-growth-factor-fgf-23-and-klotho-in-the-spleen-its-physiological-and-functional-implications
#2
Yuri Nakashima, Toru Mima, Mitsuru Yashiro, Tomohiro Sonou, Masaki Ohya, Asuka Masumoto, Shintaro Yamanaka, Daisuke Koreeda, Koichi Tatsuta, Yoshiyuki Hanba, Mari Moribata, Shigeo Negi, Takashi Shigematsu
The FGF23-Klotho signaling axis is known to exert anti-aging effects via calcium-phosphorus metabolism. In mice deficient in FGF23-Klotho signaling, however, the number of splenocytes is reduced. FGF23 is expressed in both bone and spleen, with regulation of its production differing in these organs. As FGF23-Klotho signaling may play an immunological role in the spleen, splenocytes in male C57BL/6J mice were assayed for expression of Klotho or FGF23 by flow cytometry and immunohistochemistry. Cells that expressed Klotho included CD45R/B220(+) CD21/CD35(+) CD1d(+) CD43(-) marginal zone B cells...
January 18, 2017: Growth Factors
https://www.readbyqxmd.com/read/28095507/choline-deficiency-causes-colonic-type-ii-natural-killer-t-nkt-cell-loss-and-alleviates-murine-colitis-under-type-i-nkt-cell-deficiency
#3
Shintaro Sagami, Yoshitaka Ueno, Shinji Tanaka, Akira Fujita, Hiroaki Niitsu, Ryohei Hayashi, Hideyuki Hyogo, Takao Hinoi, Yasuhiko Kitadai, Kazuaki Chayama
Serum levels of choline and its derivatives are lower in patients with inflammatory bowel disease (IBD) than in healthy individuals. However, the effect of choline deficiency on the severity of colitis has not been investigated. In the present study, we investigated the role of choline deficiency in dextran sulfate sodium (DSS)-induced colitis in mice. Methionine-choline-deficient (MCD) diet lowered the levels of type II natural killer T (NKT) cells in the colonic lamina propria, peritoneal cavity, and mesenteric lymph nodes, and increased the levels of type II NKT cells in the livers of wild-type B6 mice compared with that in mice fed a control (CTR) diet...
2017: PloS One
https://www.readbyqxmd.com/read/28091533/atp-binding-cassette-transporter-abca7-regulates-nkt-cell-development-and-function-by-controlling-cd1d-expression-and-lipid-raft-content
#4
Heba N Nowyhed, Shilpi Chandra, William Kiosses, Paola Marcovecchio, Farah Andary, Meng Zhao, Michael L Fitzgerald, Mitchell Kronenberg, Catherine C Hedrick
ABCA7 is an ABC transporter expressed on the plasma membrane, and actively exports phospholipid complexes from the cytoplasmic to the exocytoplasmic leaflet of membranes. Invariant NKT (iNKT) cells are a subpopulation of T lymphocytes that recognize glycolipid antigens in the context of CD1d-mediated antigen presentation. In this study, we demonstrate that ABCA7 regulates the development of NKT cells in a cell-extrinsic manner. We found that in Abca7(-/-) mice there is reduced expression of CD1d accompanied by an alteration in lipid raft content on the plasma membrane of thymocytes and antigen presenting cells...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28067223/the-microbiota-maintain-homeostasis-of-liver-resident-%C3%AE-%C3%AE-t-17-cells-in-a-lipid-antigen-cd1d-dependent-manner
#5
Fenglei Li, Xiaolei Hao, Yongyan Chen, Li Bai, Xiang Gao, Zhexiong Lian, Haiming Wei, Rui Sun, Zhigang Tian
The microbiota control regional immunity using mechanisms such as inducing IL-17A-producing γδ T (γδT-17) cells in various tissues. However, little is known regarding hepatic γδT cells that are constantly stimulated by gut commensal microbes. Here we show hepatic γδT cells are liver-resident cells and predominant producers of IL-17A. The microbiota sustain hepatic γδT-17 cell homeostasis, including activation, survival and proliferation. The global commensal quantity affects the number of liver-resident γδT-17 cells; indeed, E...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28062695/the-clonal-invariant-nkt-cell-repertoire-in-people-with-type-1-diabetes-is-characterized-by-a-loss-of-clones-expressing-high-affinity-tcrs
#6
Anna S Tocheva, Salah Mansour, Tristan G H Holt, Samuel Jones, Andrew Chancellor, Joseph P Sanderson, Efrem Eren, Tim J Elliott, Richard I G Holt, Stephan D Gadola
Invariant NKT (iNKT) cells in healthy people express iNKT-TCRs with widely varying affinities for CD1d, suggesting different roles for high- and low-affinity iNKT clones in immune regulation. However, the functional implications of this heterogeneity have not yet been determined. Functionally aberrant iNKT responses have been previously demonstrated in different autoimmune diseases, including human type 1 diabetes, but their relationship to changes in the iNKT clonal repertoire have not been addressed. In this study, we directly compared the clonal iNKT repertoire of people with recent onset type 1 diabetes and age- and gender-matched healthy controls with regard to iNKT-TCR affinity and cytokine production...
January 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28061947/b-lymphocytes-forming-follicle-like-structures-in-the-lung-tissue-of-tuberculosis-infected-mice-dynamics-phenotypes-and-functional-activity
#7
Irina Linge, Alexander Dyatlov, Elena Kondratieva, Vadim Avdienko, Alexander Apt, Tatiana Kondratieva
During tuberculosis (TB) infection, B cells form follicles in close vicinity of lung granuloma. We assessed the dynamics of follicle formation, surface phenotypes and functional activity of lung B cells during TB course in genetically susceptible mice. The follicles appeared early post infection and peaked at weeks 7-8. Lung B cells resembled classical B2 cells (CD19(+)IgMloIgD(hi)CD1d(-)CD21/35(int)CD5(-)CD11b(-)CD43(-)), but differed from them by the absence of B2 marker CD23. Lung B-cells constitutively expressed MHC II molecules, presented mycobacterial antigens to immune CD4(+) T-cells and produced high amounts of IL-6 and IL-11, but no classical type 1 (TNF-α, IFN-γ), or anti-inflammatory (IL-10, TGF-β) cytokines...
January 2017: Tuberculosis
https://www.readbyqxmd.com/read/28012583/nkt-cells-in-leishmaniasis
#8
Jaime Zamora-Chimal, Joselín Hernández-Ruiz, Ingeborg Becker
The role of NKT cells in the resistance or susceptibility towards Leishmania infections remains to be defined, since controversial data persist. The response of these cells seems to depend on many variables such as the infection site, the number of infecting parasites, the virulence of the strain and the Leishmania species. We here revise the activation pathways leading to NKT cell activation. NKT cells can be activated by the direct pathway, in which Leishmania glycolipids are presented by CD1d molecules on antigen presenting cells, such as dendritic cells (DC), leading to the secretion of diverse cytokines by NKT...
December 5, 2016: Immunobiology
https://www.readbyqxmd.com/read/28003380/control-of-circulating-ige-by-the-vitamin-d-receptor-in-vivo-involves-b-cell-intrinsic-and-extrinsic-mechanisms
#9
Jamaal James, Veronika Weaver, Margherita T Cantorna
Vitamin D deficiency is associated with the development of asthma and allergy. The active form of vitamin D [1,25(OH)2D] regulates B cells in vitro and mice without the vitamin D receptor (VDR knockout [KO]) have high serum IgE. Whole-body VDR KO, T cell-specific VDR (T-VDR) KO, B cell-specific VDR (B-VDR) KO, and vitamin D deficient mice were used to determine the targets of vitamin D in the regulation of IgE in vivo. Vitamin D deficient, VDR KO, and B-VDR KO mice developed hyper-IgE, whereas T-VDR KO mice did not...
December 21, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28003379/key-residues-at-third-cdr3%C3%AE-position-impact-structure-and-antigen-recognition-of-human-invariant-nk-tcrs
#10
Kenji Chamoto, Tingxi Guo, Stephen W Scally, Yuki Kagoya, Mark Ancruzowski, Chung-Hsi Wang, Muhammed A Rahman, Kayoko Saso, Marcus O Butler, Priscilla P L Chiu, Jean-Philippe Julien, Naoto Hirano
The human invariant NK (iNK) TCR is largely composed of the invariant TCR Vα24-Jα18 chain and semivariant TCR Vβ11 chains with variable CDR3β sequences. The direct role of CDR3β in Ag recognition has been studied extensively. Although it was noted that CDR3β can interact with CDR3α, how this interaction might indirectly influence Ag recognition is not fully elucidated. We observed that the third position of Vβ11 CDR3 can encode an Arg or Ser residue as a result of somatic rearrangement. Clonotypic analysis of the two iNK TCR types with a single amino acid substitution revealed that the staining intensity by anti-Vα24 Abs depends on whether Ser or Arg is encoded...
December 21, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27994954/communication-between-natural-killer-t-cells-and-adipocytes-in-obesity
#11
Masashi Satoh, Kazuya Iwabuchi
Adipose tissue contains various types of immunocompetent cells, and these cells of innate and adaptive immunity control adipose tissue inflammation that blunts insulin sensitivity. Recent studies have shown that adipocytes express CD1d and present lipid antigen(s) to activate natural killer T (NKT) cells. The function of adipocytes is in turn modulated by cytokines that NKT cells produce to alter the expression of anti-inflammatory adipokine(s) and the production of inflammatory and chemoattractant cytokines...
October 2016: Adipocyte
https://www.readbyqxmd.com/read/27901484/gene-expression-profiling-of-hematologic-malignant-cell-lines-resistant-to-oncolytic-virus-treatment
#12
Nam Hee Lee, Mikyung Kim, Sung Yong Oh, Seong-Geun Kim, Hyuk-Chan Kwon, Tae-Ho Hwang
Pexa-Vec (pexastimogene devacirpvec; JX-594) has emerged as an attractive tool in oncolytic virotherapy. Pexa-Vec demonstrates oncolytic and immunotherapeutic mechanisms of action. But the determinants of resistance to Pexa-Vec are mostly unknown. We treated hemoatologic malignant cells with Pexa-Vec and examined the gene-expression pattern of sensitive and resistant cells. Human myeloid malignant cell lines (RPMI-8226, IM-9, K562, THP-1) and lymphoid cancer cell lines (MOLT4, CCRF-CEM, Ramos, U937) were treated with Pexa-Vec...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27869820/tet-proteins-regulate-the-lineage-specification-and-tcr-mediated-expansion-of-inkt-cells
#13
Ageliki Tsagaratou, Edahí González-Avalos, Sini Rautio, James P Scott-Browne, Susan Togher, William A Pastor, Ellen V Rothenberg, Lukas Chavez, Harri Lähdesmäki, Anjana Rao
TET proteins oxidize 5-methylcytosine in DNA to 5-hydroxymethylcytosine and other oxidation products. We found that simultaneous deletion of Tet2 and Tet3 in mouse CD4(+)CD8(+) double-positive thymocytes resulted in dysregulated development and proliferation of invariant natural killer T cells (iNKT cells). Tet2-Tet3 double-knockout (DKO) iNKT cells displayed pronounced skewing toward the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPOK...
January 2017: Nature Immunology
https://www.readbyqxmd.com/read/27869818/tcr%C3%AE-tcr%C3%AE-pairing-controls-recognition-of-cd1d-and-directs-the-development-of-adipose-nkt-cells
#14
Joshua A Vieth, Joy Das, Fanomezana M Ranaivoson, Davide Comoletti, Lisa K Denzin, Derek B Sant'Angelo
The interaction between the T cell antigen receptor (TCR) expressed by natural killer T cells (NKT cells) and the antigen-presenting molecule CD1d is distinct from interactions between the TCR and major histocompatibility complex (MHC). Our molecular modeling suggested that a hydrophobic patch created after TCRα-TCRβ pairing has a role in maintaining the conformation of the NKT cell TCR. Disruption of this patch ablated recognition of CD1d by the NKT cell TCR but not interactions of the TCR with MHC. Partial disruption of the patch, while permissive to the recognition of CD1d, significantly altered NKT cell development, which resulted in the selective accumulation of adipose-tissue-resident NKT cells...
January 2017: Nature Immunology
https://www.readbyqxmd.com/read/27863541/cellular-endocytic-compartment-localization-of-expressed-canine-cd1-molecules
#15
Mette Schjaerff, Stefan M Keller, Verena K Affolter, Annemarie T Kristensen, Peter F Moore
CD1 molecules are glycoproteins present primarily on dendritic cells (DCs), which recognize and present a variety of foreign- and self-lipid antigens to T-cells. Humans have five different CD1 isoforms that survey distinct cellular compartments allowing for recognition of a large repertoire of lipids. The canine CD1 family consists of seven functional CD1 molecules (canine CD1a2, CD1a6, CD1a8, CD1a9, CD1b, CD1c and CD1e) and one presumed non-functional isoform (canine CD1d) due to a disrupted gene structure...
December 2016: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/27863214/type-ii-natural-killer-t-cells-that-recognize-sterol-carrier-protein-2-are-implicated-in-vascular-inflammation-in-the-rat-model-of-systemic-connective-tissue-diseases
#16
Yusuke Nishioka, Madoka Yamaguchi, Ai Kawakami, Maya Munehiro, Sakiko Masuda, Utano Tomaru, Akihiro Ishizu
We previously generated a rat model that developed systemic connective tissue diseases, including synovitis, myositis, and small-vessel vasculitis (SVV), and established a vascular endothelial cell-reactive T-cell clone, VASC-1, from the model. VASC-1 was determined to be a type II natural killer T-cell clone. In this study, we attempted to identify the antigen recognized by VASC-1. The monkey-derived cell line COS-7 was used because VASC-1 does not bind naturally to COS-7, although the amino acid sequences are well conserved between monkey CD1d and rat CD1d...
January 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/27837018/role-of-dendritic-cell-maturation-factors-produced-by-human-invariant-nkt-cells-in-immune-tolerance
#17
Hyeong-Woo Lee, Hyun Bae Jie, Paul L Bollyky, David Sarracino, Tong-Soo Kim, Brian S Wilson
In this study, we used the culture supernatant of iNKT cells to identify human myeloid DC maturation factors produced by human CD4(+) iNKT cells. S100A8 had a strong maturation effect. Notably, the recombinant S100A8 protein displayed properties of DC maturation functioning, and the induction of DC differentiation by both the purified and the recombinant protein were blocked by anti-S100A8 and anti-TLR-4 mAbs. DC differentiation induced by anti-major histocompatibility complex class II/CD1d Ab, S100A8, or both was qualitatively indistinguishable from that induced by the coculture of DCs and iNKT cells or via culture supplementation with supernatants from activated CD4(+) iNKT cells...
November 11, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27821872/enterogenous-bacterial-glycolipids-are-required-for-the-generation-of-natural-killer-t-cells-mediated-liver-injury
#18
Yingfeng Wei, Benhua Zeng, Jianing Chen, Guangying Cui, Chong Lu, Wei Wu, Jiezuan Yang, Hong Wei, Rufeng Xue, Li Bai, Zhi Chen, Lanjuan Li, Kazuya Iwabuchi, Toshimitsu Uede, Luc Van Kaer, Hongyan Diao
Glycolipids are potent activator of natural killer T (NKT) cells. The relationship between NKT cells and intestinal bacterial glycolipids in liver disorders remained unclear. We found that, in sharp contrast to specific pathogen-free (SPF) mice, germ-free (GF) mice are resistant to Concanavalin A (ConA)-induced liver injury. ConA treatment failed to trigger the activation of hepatic NKT cells in GF mice. These defects correlated with the sharply reduced levels of CD1d-presented glycolipid antigens in ConA-treated GF mice compared with SPF counterparts...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27801602/a-potent-adjuvant-effect-of-a-cd1d-binding-nkt-cell-ligand-in-human-immune-system-mice
#19
Xiangming Li, Jing Huang, Izumi Kaneko, Min Zhang, Shiroh Iwanaga, Masao Yuda, Moriya Tsuji
OBJECTIVES: A CD1d-binding invariant natural killer T (iNKT)-cell stimulatory glycolipid, namely 7DW8-5, is shown to enhance the efficacy of radiation-attenuated sporozoites (RAS)-based malaria vaccine in mice. In the current study, we aim to determine whether 7DW8-5 can display a potent adjuvant effect in human immune system (HIS) mice. METHODS: HIS-A2/hCD1d mice, which possess both functional human iNKT cells and CD8+ T cells, were generated by the transduction of NSG mice with adeno-associated virus serotype 9 expressing genes that encode human CD1d molecules and HLA-A*0201, followed by the engraftment of human hematopoietic stem cells...
January 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/27799307/nkt-cell-deficient-mice-harbor-an-altered-microbiota-that-fuels-intestinal-inflammation-during-chemically-induced-colitis
#20
Thirumahal Selvanantham, Qiaochu Lin, Cynthia Xinyi Guo, Anuradha Surendra, Stephanie Fieve, Nichole K Escalante, David S Guttman, Catherine J Streutker, Susan J Robertson, Dana J Philpott, Thierry Mallevaey
NKT cells are unconventional T cells that respond to self and microbe-derived lipid and glycolipid Ags presented by the CD1d molecule. Invariant NKT (iNKT) cells influence immune responses in numerous diseases. Although only a few studies have examined their role during intestinal inflammation, it appears that iNKT cells protect from Th1-mediated inflammation but exacerbate Th2-mediated inflammation. Studies using iNKT cell-deficient mice and chemically induced dextran sodium sulfate (DSS) colitis have led to inconsistent results...
October 31, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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