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NKT cells

Lun Cai, Lei Yu, Sa Liu, Tongxun Li, Xiaoping Zhang, Wei Cui, Jie Du, Qinyi Zhang
Accumulating evidence shows that immune cells play an important role in carotid atherosclerotic plaque development. In this study, we assessed the association of 6 different natural killer T (NKT) cell subsets, based on CD57 and CD8 expression, with risk for development of carotid atherosclerotic plaque (CAP). Molecular expression by peripheral NKT cells was evaluated in 13 patients with high-risk CAP and control without carotid stenosis (n = 18). High-risk CAP patients, compared with healthy subjects, had less percentage of CD57+CD8- NKT cell subsets (8...
October 24, 2016: Inflammation
Aranzazu Cruz-Adalia, Esteban Veiga
During infections, the first reaction of the host against microbial pathogens is carried out by innate immune cells, which recognize conserved structures on pathogens, called pathogen-associated molecular patterns. Afterward, some of these innate cells can phagocytose and destroy the pathogens, secreting cytokines that would modulate the immune response to the challenge. This rapid response is normally followed by the adaptive immunity, more specific and essential for a complete pathogen clearance in many cases...
2016: Frontiers in Immunology
Greg Hodge, Eugene Roscioli, Hubertus Jersmann, Hai B Tran, Mark Holmes, Paul N Reynolds, Sandra Hodge
BACKGROUND: Corticosteroid resistance is a major barrier to effective treatment of COPD. We have shown that the resistance is associated with decreased expression of glucocorticoid receptor (GCR) by senescent CD28nullCD8+ pro-inflammatory lymphocytes in peripheral blood of COPD patients. GCR must be bound to molecular chaperones heat shock proteins (Hsp) 70 and Hsp90 to acquire a high-affinity steroid binding conformation, and traffic to the nucleus. We hypothesized a loss of Hsp70/90 from these lymphocytes may further contribute to steroid resistance in COPD...
October 21, 2016: Respiratory Research
Sreya Bagchi, Sha Li, Chyung-Ru Wang
Adoptive immunotherapy for cancer treatment is an emerging field of study. Till now, several tumor-derived, peptide-specific T cell responses have been harnessed for treating cancers. However, the contribution of lipid-specific T cells in tumor immunity has been understudied. CD1 molecules, which present self- and foreign lipid antigens to T cells, are divided into group 1 (CD1a, CD1b, and CD1c) and group 2 (CD1d). Although the role of CD1d-restricted natural killer T cells (NKT) in several tumor models has been well established, the contribution of group 1 CD1-restricted T cells in tumor immunity remains obscure due to the lack of group 1 CD1 expression in mice...
2016: Oncoimmunology
M-T Rubio, M Bouillié, N Bouazza, T Coman, H Trebeden-Nègre, A Gomez, F Suarez, D Sibon, A Brignier, E Paubelle, S Nguyen-Khoc, M Cavazzana, O Lantz, M Mohty, S Urien, O Hermine
Clinically useful pre-transplant predictive factors of acute graft-versus-host-disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT) are lacking. We prospectively analyzed HSC graft content in CD34(+), NK, conventional T, regulatory T and invariant NKT (iNKT) cells in 117 adult patients before allo-SCT. Results were correlated with occurrence of aGVHD and relapse. In univariate analysis, iNKT cells were the only graft cell populations associated with occurrence of aGVHD. In multivariate analysis, CD4(-) iNKT/T cell frequency could predict grade II-IV aGVHD in bone marrow and peripheral blood stem cell (PBSC) grafts, while CD4(-) iNKT expansion capacity was predictive in PBSC grafts...
October 14, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Carolyn Tubby, Ola H Negm, Timothy Harrison, Patrick J Tighe, Ian Todd, Lucy C Fairclough
OBJECTIVE: The three main types of killer cells - CD8(+) T cells, NK cells and NKT cells - have been linked to asthma and chronic obstructive pulmonary disease (COPD). However, their role in a small subset of asthma patients displaying fixed airway obstruction (FAO), similar to that seen in COPD, has not been explored. The objective of the present study was to investigate killer cell numbers, phenotype and function in peripheral blood from asthma patients with FAO, asthma patients without FAO, and healthy individuals...
October 13, 2016: Journal of Asthma: Official Journal of the Association for the Care of Asthma
Daniel M Vasconcelos, Raquel M Gonçalves, Catarina R Almeida, Inês O Pereira, Marta I Oliveira, Nuno Neves, Andreia M Silva, António C Ribeiro, Carla Cunha, Ana R Almeida, Cristina C Ribeiro, Ana M Gil, Elisabeth Seebach, Katharina L Kynast, Wiltrud Richter, Meriem Lamghari, Susana G Santos, Mário A Barbosa
The hypothesis behind this work is that fibrinogen (Fg), classically considered a pro-inflammatory protein, can promote bone repair/regeneration. Injury and biomaterial implantation naturally lead to an inflammatory response, which should be under control, but not necessarily minimized. Herein, porous scaffolds entirely constituted of Fg (Fg-3D) were implanted in a femoral rat bone defect and investigated at two important time points, addressing the bone regenerative process and the local and systemic immune responses, both crucial to elucidate the mechanisms of tissue remodelling...
December 2016: Biomaterials
Masashi Satoh, Ken-Ichi Namba, Nobuyoshi Kitaichi, Noriko Endo, Hirokuni Kitamei, Daiju Iwata, Shigeaki Ohno, Susumu Ishida, Kazunori Onoé, Hiroshi Watarai, Masaru Taniguchi, Tatsuro Ishibashi, Joan Stein-Streilein, Koh-Hei Sonoda, Luc Van Kaer, Kazuya Iwabuchi
Experimental autoimmune uveoretinitis (EAU) represents an experimental model for human endogenous uveitis, which is caused by Th1/Th17 cell-mediated inflammation. Natural killer T (NKT) cells recognize lipid antigens and produce large amounts of cytokines upon activation. To examine the role of NKT cells in the development of uveitis, EAU was elicited by immunization with a peptide from the human interphotoreceptor retinoid-binding protein (hIRBP1-20) in complete Freund's adjuvant and histopathology scores were evaluated in C57BL/6 (WT) and NKT cell-deficient mice...
October 5, 2016: Experimental Eye Research
Na Li, Jinlian Hua
After partial hepatectomy, hepatocytes proliferate to restore mass and function of the liver. Macrophages, natural killer (NK) cells, natural killer T (NKT) cells, dendritic cells (DC), eosinophils, gamma delta T (γδT) cells, and conventional T cells, as well as other subsets of the immune cells residing in the liver control liver regeneration, either through direct interactions with hepatocytes or indirectly by releasing inflammatory cytokines. Here, we review recent progress regarding the immune cells in the liver and their functions during liver regeneration...
September 27, 2016: Oncotarget
Hui-Fern Koay, Nicholas A Gherardin, Anselm Enders, Liyen Loh, Laura K Mackay, Catarina F Almeida, Brendan E Russ, Claudia A Nold-Petry, Marcel F Nold, Sammy Bedoui, Zhenjun Chen, Alexandra J Corbett, Sidonia B G Eckle, Bronwyn Meehan, Yves d'Udekem, Igor E Konstantinov, Martha Lappas, Ligong Liu, Chris C Goodnow, David P Fairlie, Jamie Rossjohn, Mark M Chong, Katherine Kedzierska, Stuart P Berzins, Gabrielle T Belz, James McCluskey, Adam P Uldrich, Dale I Godfrey, Daniel G Pellicci
Mucosal-associated invariant T cells (MAIT cells) detect microbial vitamin B2 derivatives presented by the antigen-presenting molecule MR1. Here we defined three developmental stages and checkpoints for the MAIT cell lineage in humans and mice. Stage 1 and stage 2 MAIT cells predominated in thymus, while stage 3 cells progressively increased in abundance extrathymically. Transition through each checkpoint was regulated by MR1, whereas the final checkpoint that generated mature functional MAIT cells was controlled by multiple factors, including the transcription factor PLZF and microbial colonization...
September 26, 2016: Nature Immunology
Tatsuya Ando, Hiroyasu Ito, Hirofumi Ohtaki, Ayumu Kanbe, Akihiro Hirata, Akira Hara, Mitsuru Seishima
Viral infections can give rise to secondary bacterial infections. In the present study, we examined the role of invariant natural killer T (iNKT) cells in lipopolysaccharide (LPS)-induced lethal shock during encephalomyocarditis virus (EMCV) infection. Wild-type (WT) mice and Jα18 gene knockout (Jα18 KO) mice were inoculated with EMCV, 5days prior to challenging with LPS. The survival rate of Jα18 KO mice subjected to EMCV and LPS was significantly higher than that of WT mice. TNF-α and nitric oxide (NO) production were increased in WT mice, than that in Jα18 KO mice, after the administration of EMCV and LPS...
September 19, 2016: Immunobiology
Xilin Zhang, Jun Gu, Li Zhou, Qing-Sheng Mi
T cell immunoglobulin and mucin-4 (TIM-4), mainly expressed on antigen presenting cells, plays a versatile role in immunoregulation. CD1d-restricted invariant natural killer T (iNKT) cells are potent cells involved in the diverse immune responses. It was recently reported that recombinant TIM-4 (rTIM-4) alone enhanced cytokine production in NKT hybridoma, DN32.D3 cells. Hence, we hypothesized that TIM-4 might regulate iNKT cell biology, especially their function of cytokine secretion. For the first time, we identified that TIM-4 was expressed in thymus iNKT cells, and its expression increased upon iNKT cell migration to the secondary lymphoid organs, especially in lymph nodes...
September 20, 2016: Oncotarget
Shiori Takashima, Kenichi Ikejima, Kumiko Arai, Junko Yokokawa, Kazuyoshi Kon, Shunhei Yamashina, Sumio Watanabe
Strategies for prevention and treatment of nonalcoholic steatohepatitis (NASH) remain to be established. Here, we evaluated the effect of glycine on metabolic steatohepatitis in genetically obese, diabetic KK-A(y) mice. Male KK-A(y) mice were fed a diet containing 5% glycine for 4 weeks, and liver pathology was evaluated. Hepatic mRNA levels for lipid-regulating molecules, cytokines/chemokines, and macrophage M1/M2 markers were determined by real time RT-PCR. Hepatic expression of natural killer (NK) T cells was analyzed by flow cytometry...
September 22, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Shinsuke Inuki, Toshihiko Aiba, Natsumi Hirata, Osamu Ichihara, Daisuke Yoshidome, Shunsuke Kita, Katsumi Maenaka, Koichi Fukase, Yukari Fujimoto
The CD1d protein is a nonpolymorphic MHC class I-like protein that controls the activation of natural killer T (NKT) cells through the presentation of self- and foreign-lipid ligands, glycolipids, or phospholipids, leading to the secretion of various cytokines. The CD1d contains a large hydrophobic lipid binding pocket: the A' pocket of CD1d, which recognizes hydrophobic moieties of the ligands, such as long fatty acyl chains. Although lipid-protein interactions typically rely on hydrophobic interactions between lipid chains and the hydrophobic sites of proteins, we showed that the small polar regions located deep inside the hydrophobic A' pocket could be used for the modulation of the lipid binding...
October 4, 2016: ACS Chemical Biology
Chao Hu, Chao Zhang, Cheng Yang
Acute kidney injury (AKI) is manifested by inflammation, and an early feature in the pathogenesis is the accumulation of immune cells in the kidney. Natural killer T (NKT) cells, a peculiar T cells subtype, serve as a bridge between innate and adaptive immunity. Due to the difference between type I and type II subsets, NKT cells were supposed to play a dual role in IR-related tissue injury. Furthermore, membrane receptors and clinical immunosuppressive agents remain involved in the modulation of NKT cell function...
September 9, 2016: Current Protein & Peptide Science
Ana Lleo, Zhaolian Bian, Haiyan Zhang, Qi Miao, Fang Yang, Yanshen Peng, Xiaoyu Chen, Ruqi Tang, Qixia Wang, Dekai Qiu, Jingyuan Fang, Cristina Sobacchi, Anna Villa, Luca Di Tommaso, Massimo Roncalli, M Eric Gershwin, Xiong Ma, Pietro Invernizzi
There is substantial data that suggests an abnormality of innate immunity in patients with primary biliary cholangitis (PBC) which includes the transcription factor nuclear factor-kB (NF-kB) and well as downstream inflammatory signaling pathways. In addition, ImmunoChip analysis has identified a novel PBC-associated locus near the receptor activator of NF-kB ligand (RANKL) gene. Based on these observations, we investigated the role of the RANKL axis in the liver of patients with PBC compared to controls. We used immunohistochemistry to quantitate liver expression of RANKL, its receptor (RANK), and importantly the decoy receptor osteoprotegerin (OPG), including a total of 122 liver samples (PBC = 37, primary sclerosing cholangitis = 20, autoimmune hepatitis = 26, chronic hepatitis B = 32 and unaffected controls = 7)...
2016: PloS One
Marta Cossu, Lenny van Bon, Stefan Nierkens, Chiara Bellocchi, Alessandro Santaniello, Harry Dolstra, Lorenzo Beretta, Timothy R D J Radstake
Immune activation is a hallmark of systemic sclerosis (SSc). However, the immunological alterations that occur in preclinical and non-fibrotic SSc and that differentiate these subjects from those with primary Raynaud's phenomenon (PRP) or healthy controls (HC) are poorly defined. We isolated CD56+ (NK/NKT-like) cells from HC, patients with PRP, early SSc (EaSSc) and definite SSc without skin or lung fibrosis. Cytokine production upon different activating stimuli was measured via a multiplex immuno assay. Clearly discriminative patterns among the different stages of SSc were most markedly observed after TLR1/2 stimulation, with increased IL-6, TNF-α and MIP-1α/CCL3 production in definite SSc patients as compared to HC and/or PRP...
September 8, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Irina V Tiper, Tonya J Webb
Histone deacetylases (HDACs) are a family of enzymes that influence expression of genes implicated in tumor initiation, progression, and anti-tumor responses. In addition to their canonical role in deacetylation of histones, HDACs regulate many non-canonical targets, such as Signal Transducer and Activator of Transcription 3 (STAT3). We hypothesize that tumors use epigenetic mechanisms to dysregulate CD1d-mediated antigen presentation, thereby impairing the ability of natural killer T (NKT) cells to recognize and destroy malignant cells...
September 10, 2016: Cancer Immunology, Immunotherapy: CII
Savit B Prabhu, Deepak K Rathore, Deepa Nair, Anita Chaudhary, Saimah Raza, Parna Kanodia, Shailaja Sopory, Anna George, Satyajit Rath, Vineeta Bal, Reva Tripathi, Siddharth Ramji, Aruna Batra, Kailash C Aggarwal, Harish K Chellani, Sugandha Arya, Nidhi Agarwal, Umesh Mehta, Uma Chandra Mouli Natchu, Nitya Wadhwa, Shinjini Bhatnagar
The human peripheral leukocyte subset composition depends on genotype variation and pre-natal and post-natal environmental influence diversity. We quantified this composition in adults and neonates, and compared the median values and dispersal ranges of various subsets in them. We confirmed higher frequencies of monocytes and regulatory T cells (Tregs), similar frequencies of neutrophils, and lower frequencies of CD8 T cells, NKT cells, B1 B cells and gamma-delta T cells in neonatal umbilical cord blood. Unlike previous reports, we found higher frequencies of eosinophils and B cells, higher CD4:CD8 ratios, lower frequencies of T cells and iNKT cells, and similar frequencies of CD4 T cells and NK cells in neonates...
2016: PloS One
Matthias Hauptmann, Julia Kolbaum, Stefanie Lilla, David Wozniak, Mohammad Gharaibeh, Bernhard Fleischer, Christian A Keller
T cells are known to contribute to immune protection against scrub typhus, a potentially fatal infection caused by the obligate intracellular bacterium Orientia (O.) tsutsugamushi. However, the contribution of CD8+ T cells to protection and pathogenesis during O. tsutsugamushi infection is still unknown. Using our recently developed BALB/c mouse model that is based on footpad inoculation of the human-pathogenic Karp strain, we show that activated CD8+ T cells infiltrate spleen and lung during the third week of infection...
September 2016: PLoS Neglected Tropical Diseases
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