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https://www.readbyqxmd.com/read/28102966/histone-deacetylase-2-is-decreased-in-peripheral-blood-pro-inflammatory-cd8-t-and-nkt-like-lymphocytes-following-lung-transplant
#1
Greg Hodge, Sandra Hodge, Chien-Li Holmes-Liew, Paul N Reynolds, Mark Holmes
BACKGROUND AND OBJECTIVE: Immunosuppression therapy following lung transplantation fails to prevent chronic rejection in many patients, which is associated with lack of suppression of cytotoxic mediators and pro-inflammatory cytokines in peripheral blood T and natural killer T (NKT)-like cells. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) upregulate/downregulate pro-inflammatory gene expression, respectively; however, differences in the activity of these enzymes following lung transplant are unknown...
February 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28096089/tolerogenic-interactions-between-cd8-dendritic-cells-and-nkt-cells-prevent-rejection-of-bone-marrow-and-organ-grafts
#2
David Hongo, Xiaobin Tang, Xiangyue Zhang, Edgar G Engleman, Samuel Strober
The combination of total lymphoid irradiation and anti-T cell antibodies safely induces immune tolerance to combined hematopoietic cell and organ allografts in humans. Our mouse model required host natural killer T (NKT) cells to induce tolerance. Since NKT cells normally depend on signals from CD8+ dendritic cells (DCs) for their activation, we used the mouse model to test the hypothesis that after lymphoid irradiation host CD8+DCs play a requisite role in tolerance induction through interactions with NKT cells...
January 17, 2017: Blood
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/28095355/immune-regulatory-network-in-successful-pregnancy-and-reproductive-failures
#4
REVIEW
Mahnaz Ghaebi, Mohammad Nouri, Aliyeh Ghasemzadeh, Laya Farzadi, Farhad Jadidi-Niaragh, Majid Ahmadi, Mehdi Yousefi
Maternal immune system must tolerate semiallogenic fetus to establish and maintain a successful pregnancy. Despite the existence of several strategies of trophoblast to avoid recognition by maternal leukocytes, maternal immune system may react against paternal alloantigenes. Leukocytes are important components in decidua. Not only T helper (Th)1/Th2 balance, but also regulatory T (Treg) cells play an important role in pregnancy. Although the frequency of Tregs is elevated during normal pregnancies, their frequency and function are reduced in reproductive defects such as recurrent miscarriage and preeclampsia...
January 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28093832/il-15-deficient-mice-develop-enhanced-allergic-responses-to-airway-allergen-exposure
#5
Clinton B Mathias, Craig M Schramm, Linda A Guernsey, Carol A Wu, Stephanie H Polukort, Jeffrey Rovatti, Jennifer Ser-Dolansky, Eric Secor, Sallie S Schneider, Roger S Thrall, Hector L Aguila
BACKGROUND: Interleukin-15 is a pleiotropic cytokine that is critical for the development and survival of multiple hematopoietic lineages. Mice lacking IL-15 have selective defects in populations of several pro-allergic immune cells including natural killer (NK) cells, NKT cells, and memory CD8(+) T cells. We therefore hypothesized that IL-15(-/-) mice will have reduced inflammatory responses during the development of allergic airway disease (AAD). OBJECTIVE: To determine whether IL-15(-/-) mice have attenuated allergic responses in a mouse model of AAD...
January 17, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28092402/%C3%AE-%C3%AE-t-cells-are-indispensable-for-il-23-mediated-protection-against-cona-induced-hepatitis-in-hepatitis-b-virus-transgenic-mice
#6
Ziyu Meng, Jingya Wang, Yifang Yuan, Guangchao Cao, Shuobing Fan, Chao Gao, Li Wang, Zheng Li, Xiaoli Wu, Zhenzhou Wu, Liqing Zhao, Zhinan Yin
Hepatitis B virus surface antigen (HBsAg) carriers are highly susceptible to liver injury triggered by environmental biochemical stimulation. Previously, we have reported an inverse correlation between γδT cells and liver damage in patients with HBV. However, whether γδT cells play a role in regulating the hypersensitivity of HBsAg carriers to biochemical stimulation-induced hepatitis is unknown. In this study, using hepatitis B virus transgenic (HBs-Tg) and HBs-Tg-TCRδ(-/-) mice, we found that mice genetically deficient in γδT cells exhibited more severe liver damage upon ConcanavalinA (ConA) treatment, as indicated by substantially higher serum alanine aminotransferase (ALT) levels, further elevated IFN-γ levels and more extensive necrosis...
January 16, 2017: Immunology
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
#7
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/28078715/mtorc2-regulates-multiple-aspects-of-nkt-cell-development-and-function
#8
Tammarah Sklarz, Peng Guan, Mercy Gohil, Renee M Cotton, Moyar Q Ge, Angela Haczku, Rupali Das, Martha S Jordan
Invariant NKT (iNKT) cells bridge innate and adaptive immunity by rapidly secreting cytokines and lysing targets following TCR recognition of lipid antigens. Based on their ability to secrete IFN-γ, IL-4 and IL-17A, iNKT-cells are classified as NKT-1, NKT-2 and NKT-17 subsets, respectively. The molecular pathways regulating iNKT-cell fate are not fully defined. Recent studies implicate Rictor, a required component of mTORC2, in the development of select iNKT-cell subsets, however these reports are conflicting...
January 12, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28068397/burn-injury-leads-to-increased-long-term-susceptibility-to-respiratory-infection-in-both-mouse-models-and-population-studies
#9
Vanessa S Fear, James H Boyd, Suzanne Rea, Fiona M Wood, Janine M Duke, Mark W Fear
BACKGROUND: Burn injury initiates an acute inflammatory response that subsequently drives wound repair. However, acute disruption to the immune response is also common, leading to susceptibility to sepsis and increased morbidity and mortality. Despite increased understanding of the impact of burn injury on the immune system in the acute phase, little is known about long-term consequences of burn injury on immune function. This study was established to determine whether burn injury has long-term clinical impacts on patients' immune responses...
2017: PloS One
https://www.readbyqxmd.com/read/28063891/gm-csf-and-il-4-produced-by-nkt-cells-inversely-regulate-il-1%C3%AE-production-by-macrophages
#10
Sehee Ahn, Dongjin Jeong, Sae Jin Oh, Jiye Ahn, Seung Hyo Lee, Doo Hyun Chung
Natural Killer T (NKT) cells are distinct T cell subset that link innate and adaptive immune responses. IL-1β, produced by various immune cells, plays a key role in the regulation of innate immunity in vivo. However, it is unclear whether NKT cells regulate IL-1β production by macrophages. To address this, we co-cultured NKT cells and peritoneal macrophages in the presence of TCR stimulation and inflammasome activators. Among cytokines secreted from NKT cells, GM-CSF enhanced IL-1β production by macrophages via regulating LPS-mediated pro-IL-1β expression and NLRP3-dependent inflammasome activation, whereas IL-4 enhanced M2-differentiation of macrophages and decreased IL-1β production...
January 4, 2017: Immunology Letters
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
#11
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/28054551/innate-and-adaptive-immune-traits-are-differentially-affected-by-genetic-and-environmental-factors
#12
Massimo Mangino, Mario Roederer, Margaret H Beddall, Frank O Nestle, Tim D Spector
The diversity and activity of leukocytes is controlled by genetic and environmental influences to maintain balanced immune responses. However, the relative contribution of environmental compared with genetic factors that affect variations in immune traits is unknown. Here we analyse 23,394 immune phenotypes in 497 adult female twins. 76% of these traits show a predominantly heritable influence, whereas 24% are mostly influenced by environment. These data highlight the importance of shared childhood environmental influences such as diet, infections or microbes in shaping immune homeostasis for monocytes, B1 cells, γδ T cells and NKT cells, whereas dendritic cells, B2 cells, CD4(+) T and CD8(+) T cells are more influenced by genetics...
January 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28049627/dissection-of-sap-dependent-and-sap-independent-slam-family-signaling-in-nkt-cell-development-and-humoral-immunity
#13
Shasha Chen, Chenxu Cai, Zehua Li, Guangao Liu, Yuande Wang, Marzenna Blonska, Dan Li, Juan Du, Xin Lin, Meixiang Yang, Zhongjun Dong
Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) mutations in X-linked lymphoproliferative disease (XLP) lead to defective NKT cell development and impaired humoral immunity. Because of the redundancy of SLAM family receptors (SFRs) and the complexity of SAP actions, how SFRs and SAP mediate these processes remains elusive. Here, we examined NKT cell development and humoral immunity in mice completely deficient in SFR. We found that SFR deficiency severely impaired NKT cell development...
January 3, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28035011/invariant-nkt-cells-are-pathogenic-in-the-hla-dr4-transgenic-humanized-mouse-model-of-toxic-shock-syndrome-and-can-be-targeted-to-reduce-morbidity
#14
Peter A Szabo, Patrick T Rudak, Joshua Choi, Stacey X Xu, Robert Schaub, Bhagirath Singh, John K McCormick, S M Mansour Haeryfar
During toxic shock syndrome (TSS), bacterial superantigens trigger a polyclonal T cell response leading to a potentially catastrophic 'cytokine storm'. Whether innate-like invariant natural killer T(iNKT) cells, with remarkable immunomodulatory properties, participate in TSS is unclear. Using genetic and cell depletion approaches, we generated iNKT cell-deficient, superantigen-sensitive HLA-DR4-transgenic (DR4tg) mice, which were compared with their iNKT-sufficient counterparts for responsiveness to staphylococcal enterotoxin B(SEB)...
December 29, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28030343/anti-anisakis-sp-antibodies-in-serum-of-healthy-subjects-relationship-with-%C3%AE-%C3%AE-and-%C3%AE-%C3%AE-t-cells
#15
Vega Zamora, Carlos García-Ballesteros, Carmen Benet-Campos, Ferrán Ballester, Carmen Cuéllar, Juan C Andreu-Ballester
Anisakiosis is nowadays one of the nematodoses more prevalent in Spain, with rates that oscillate between 0.43% in Galicia (N.W. Spain), and 15.7% and 22.1% in inland and southern regions, respectively. Likewise, it has been proved that Anisakis larvae have developed mechanisms to modulate the dichotomy of the host immune response for their own benefit. The experimental hypothesis of the present study was that Anisakis sp. larval products can be mediators of immune suppression and induce changes on the populations of αβ+ and γδ+ T cells...
March 1, 2017: Acta Parasitologica
https://www.readbyqxmd.com/read/28029652/tumor-suppressor-blu-promotes-trail-induced-apoptosis-by-downregulating-nf-%C3%AE%C2%BAb-signaling-in-nasopharyngeal-carcinoma
#16
Jiahui Zhou, Zunnan Huang, Ziyou Wang, Shumin Liu, Alf Grandien, Ingemar Ernberg, Zhiwei He, Xiangning Zhang
A putative tumor suppressor BLU mapped on the chromosomal 3p21 region, is frequently lost in human tumors including nasopharyngeal carcinoma (NPC). To explore the underlying mechanism of tumor suppression by BLU, its potential to promote apoptosis induced by TRAIL, an effector molecule elaborated by natural killer-T (NKT) cells was investigated. BLU was re-expressed in NPC-derived HNE1 cells by recombinant adenoviral infection and the cells were challenged with recombinant TRAIL. The growth inhibition of BLU was assayed and apoptosis was examined by flow cytometry-based tetramethylrhodamine ethyl ester (TMRE) and annexin V staining, cleavage of pro-caspase-8 and poly ADP ribose polymerase (PARP)...
December 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/28025136/cd3-cd56-natural-killer-t-cell-activity-in-children-with-different-forms-of-juvenile-idiopathic-arthritis-and-the-influence-of-etanercept-treatment-on-polyarticular-subgroup
#17
Juan Zhou, Yuan Ding, Yu Zhang, Ye Feng, Xuemei Tang, Xiaodong Zhao
Juvenile idiopathic arthritis (JIA) has three major onset types with widely varying clinical features. We assessed the natural killer T (NKT) cell function in patients with different JIA subtypes, and found systemic patients exhibited lower NKT cell counts, perforin and granzyme B expression, while the pauciarticular and polyarticular patients displayed higher perforin and granzyme B expression as compared with the controls. The synovial fluid had more NKT cells with higher levels of perforin, granzyme B, and tumour necrosis factor (TNF)-α than peripheral cells...
December 24, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28012583/nkt-cells-in-leishmaniasis
#18
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/28003379/key-residues-at-third-cdr3%C3%AE-position-impact-structure-and-antigen-recognition-of-human-invariant-nk-tcrs
#19
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/27995420/lactic-acid-in-tumor-microenvironments-causes-dysfunction-of-nkt-cells-by-interfering-with-mtor-signaling
#20
Di Xie, Shasha Zhu, Li Bai
Cellular metabolism has been shown to regulate differentiation and function of immune cells. Tumor associated immune cells undergo phenotypic and functional alterations due to the change of cellular metabolism in tumor microenvironments. NKT cells are good candidates for immunotherapies against tumors and have been used in several clinical trials. However, the influences of tumor microenvironments on NKT cell functions remain unclear. In our studies, lactic acid in tumor microenvironments inhibited IFNγ and IL4 productions from NKT cells, and more profound influence on IFNγ was observed...
December 2016: Science China. Life Sciences
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