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nkt cells and obesity

Tomasz J Guzik, Dominik S Skiba, Rhian M Touyz, David G Harrison
Adipose tissue (AT) dysfunction, characterized by loss of its homeostatic functions, is a hallmark of non-communicable diseases. It is characterized by chronic low-grade inflammation and is observed in obesity, metabolic disorders such as insulin resistance and diabetes. While classically it has been identified by increased cytokine or chemokine expression, such as increased MCP-1, RANTES, IL-6, interferon (IFN) gamma or TNFα, mechanistically, immune cell infiltration is a prominent feature of the dysfunctional AT...
July 1, 2017: Cardiovascular Research
Gloria Donninelli, Manuela Del Cornò, Marina Pierdominici, Beatrice Scazzocchio, Rosaria Varì, Barbara Varano, Ilenia Pacella, Silvia Piconese, Vincenzo Barnaba, Massimo D'Archivio, Roberta Masella, Lucia Conti, Sandra Gessani
Visceral adipose tissue (VAT) is a main site where metabolic and immunologic processes interplay to regulate, at local and systemic level, the inflammatory status and immune response. Obesity-associated inflammation and immune dysfunctions are inextricably linked to tumor but, in spite of intense efforts, the mechanisms underpinning this association remain elusive. In this report, we characterized the profile of VAT-associated and circulating innate lymphocyte and regulatory T (Treg) cell subsets underlying inflammatory conditions, such as obesity and colorectal cancer (CRC)...
2017: Frontiers in Immunology
Miao-Shang Su, Li Xu, Kang Xu, Ji-Shan Zheng
PURPOSE: The purpose of this study is to determine the role of T lymphocyte immune imbalance and interleukin (IL)-10 gene polymorphism in the development of obstructive sleep apnea (OSA) in obese children. METHODS: One hundred obese children at high-risk and low-risk for OSA based upon a sleep questionnaire were selected. Peripheral blood T lymphocyte subsets were measured by flow cytometry, and plasma IFN-γ, IL-4, and IL-10 cytokines were detected by ELISA. The relationships between OSA and the above variables were analyzed...
May 12, 2017: Sleep & Breathing, Schlaf & Atmung
Huimin Zhang, Rufeng Xue, Shasha Zhu, Sicheng Fu, Zuolong Chen, Rongbin Zhou, Zhigang Tian, Li Bai
Metaflammation is responsible for several metabolic syndromes, such as type 2 diabetes. However, the mechanisms by which metabolic disorders trigger metaflammation remain unclear. We identified a cell type-specific downregulation of CD1d expression in M2 macrophages during the progression of obesity prior to the onset of inflammation in visceral adipose tissues. A reduction in CD1d expression influenced the ability of M2 macrophages to present antigens and caused a change in antigen-presenting cells from M2 macrophages to M1 macrophages...
April 10, 2017: Cellular & Molecular Immunology
Guodong Tie, Jinglian Yan, Lyne Khair, Julia A Messina, April Deng, Joonsoo Kang, Thomas Fazzio, Louis M Messina
Obesity will soon surpass smoking as the most preventable cause of cancer. Hypercholesterolemia, a common comorbidity of obesity, has been shown to increase cancer risk, especially colorectal cancer. However, the mechanism by which hypercholesterolemia or any metabolic disorder increases cancer risk remains unknown. In this study, we show that hypercholesterolemia increases the incidence and pathologic severity of colorectal neoplasia in two independent mouse models. Hypocholesterolemia induced an oxidant stress-dependent increase in miR101c, which downregulated Tet1 in hematopoietic stem cells (HSC), resulting in reduced expression of genes critical to natural killer T cell (NKT) and γδ T-cell differentiation...
May 1, 2017: Cancer Research
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
Shiori Takashima, Kenichi Ikejima, Kumiko Arai, Junko Yokokawa, Kazuyoshi Kon, Shunhei Yamashina, Sumio Watanabe
Strategies for prevention and treatment of nonalcoholic steatohepatitis remain to be established. 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 wk, 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...
December 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Xiaofeng Ding, Yan Luo, Xing Zhang, Handong Zheng, Xin Yang, Xuexian Yang, Meilian Liu
Group 2 innate lymphoid cells (ILC2s) in white adipose tissue (WAT) promote WAT browning and assist in preventing the development of obesity. However, how ILC2 in adipose tissue is regulated remains largely unknown. Here, our study shows that ILC2s are present in brown adipose tissue (BAT) as well as subcutaneous and epididymal WAT (sWAT and eWAT). The fractions of ILC2s, natural killer T (NKT) cells and eosinophils in sWAT, eWAT and BAT are significantly decreased by high-fat-diet (HFD) feeding and leptin deficiency-induced obesity...
October 2016: Journal of Endocrinology
Nina Fransén-Pettersson, Nadia Duarte, Julia Nilsson, Marie Lundholm, Sofia Mayans, Åsa Larefalk, Tine D Hannibal, Lisbeth Hansen, Anja Schmidt-Christensen, Fredrik Ivars, Susanna Cardell, Richard Palmqvist, Björn Rozell, Dan Holmberg
Here we characterize a new animal model that spontaneously develops chronic inflammation and fibrosis in multiple organs, the non-obese diabetic inflammation and fibrosis (N-IF) mouse. In the liver, the N-IF mouse displays inflammation and fibrosis particularly evident around portal tracts and central veins and accompanied with evidence of abnormal intrahepatic bile ducts. The extensive cellular infiltration consists mainly of macrophages, granulocytes, particularly eosinophils, and mast cells. This inflammatory syndrome is mediated by a transgenic population of natural killer T cells (NKT) induced in an immunodeficient NOD genetic background...
2016: PloS One
Masashi Satoh, Miyuki Hoshino, Koki Fujita, Misao Iizuka, Satoshi Fujii, Christopher S Clingan, Luc Van Kaer, Kazuya Iwabuchi
It has been shown that CD1d expression and glycolipid-reactive, CD1d-restricted NKT cells exacerbate the development of obesity and insulin resistance in mice. However, the relevant CD1d-expressing cells that influence the effects of NKT cells on the progression of obesity remain incompletely defined. In this study, we have demonstrated that 3T3-L1 adipocytes can present endogenous ligands to NKT cells, leading to IFN-γ production, which in turn, stimulated 3T3-L1 adipocytes to enhance expression of CD1d and CCL2, and decrease expression of adiponectin...
June 22, 2016: Scientific Reports
Irene Marafini, Ivan Monteleone, Davide Di Fusco, Silvia Sedda, Maria Laura Cupi, Daniele Fina, Alessandro Omero Paoluzi, Francesco Pallone, Giovanni Monteleone
INTRODUCTION AND AIM: Natural killer (NK) cells are a first line of defence against viruses and down-regulation of NK cell cytotoxic receptors represents one of the strategies by which viruses escape the host's immune system. Since onset of celiac disease (CD), a gluten-driven enteropathy, has been associated with viral infections, we examined whether CD-associated inflammation is characterized by abnormal distribution of NK cell receptors involved in recognition of viral-infected cells...
2016: PloS One
Jacob Couturier, Neeti Agarwal, Pramod N Nehete, Wallace B Baze, Michael A Barry, K Jagannadha Sastry, Ashok Balasubramanyam, Dorothy E Lewis
BACKGROUND: HIV reservoirs pose major challenges to viral eradication. The main cellular reservoirs include CD4 T cells and macrophages, whereas anatomic reservoirs are thought to be primarily lymphoid tissues. Adipose tissue represents a potentially important non-lymphoid location for HIV replication and persistence because the stromal-vascular-fraction (AT-SVF) contains activated innate and adaptive immune cells that increase in number during infections, obesity, and chronic inflammation...
April 27, 2016: Retrovirology
Yan Luo, Meilian Liu
Adiponectin acts as a key regulator of the innate immune system and plays a major role in the progression of inflammation and metabolic disorders. Macrophages and monocytes are representative components of the innate immune system, and their proliferation, plasticity, and polarization are a key component of metabolic adaption. Innate-like lymphocytes such as group 2 innate lymphoid cells (ILC2s), natural killer T (NKT) cells, and gamma delta T (γδ T) cells are also members of the innate immune system and play important roles in the development of obesity and its related diseases...
April 2016: Journal of Molecular Cell Biology
Luis Octavio Gonzalez-Espinosa, Laura Arcelia Montiel-Cervantes, Angel Guerra-Márquez, Karina Peñaflor-Juárez, Elba Reyes-Maldonado, Jorge Vela-Ojeda
BACKGROUND: One of the major limitations of umbilical cord blood (UCB) as hematopoietic stem cell source is its restricted cell number. In mothers who are candidates for stem cell donation, there are variables that affect the quantity and quality of UCB units. The aim of this study was to determine if obstetric, maternal, and fetal factors modify the number of lymphocyte subsets in UCB units. STUDY DESIGN AND METHODS: This was a prospective, observational study...
May 2016: Transfusion
Yelei Guo, Lei Xia, Shilun Zhang, Jiang Zhong, Yu Chen
Type 1 diabetes (T1D), an autoimmune disease, can be protected against by natural killer T (NKT) cells. Several attempts demonstrate that NKT cells also can be produced by inducing with Staphylococcus enterotoxin B (SEB) in addition to its classical activated antigen α-galactosylceramide. Here, we examined a potential usage of SEB-induced T (SEB-T) cells for the treatment of T1D. We established the immunophenotypes of SEB-T cells via flow cytometry, and in consequence, enriched in CD8(+)NKT cells after SEB stimulated...
2015: Central-European Journal of Immunology
Yi-Ping Chen, Jing-Hong Zhang, Chao-Qian Li, Qi-Xiang Sun, Xiao-Hong Jiang
BACKGROUND: Obesity increases the incidence of asthma, but mechanism between asthma and obesity isn't utterly understood. NKT cells are intermediary activist between the innate and adaptive immune. It may play an equally important role in both obesity and asthma. We studied an obese mouse model of allergic asthma to test whether NKT cells act as a linkage in the development of obesity with asthma. METHODS: Balb/c mice were divided into control group (A), asthma model group (B), the obesity group (C) and obesity with asthma group (D), asthma model made by OVA...
2015: International Journal of Clinical and Experimental Medicine
Firas Alhasson, Diptadip Dattaroy, Suvarthi Das, Varun Chandrashekaran, Ratanesh Kumar Seth, Rick G Schnellmann, Saurabh Chatterjee
Obesity and nonalcoholic fatty liver disease (NAFLD) are associated with the development and progression of chronic kidney disease. We recently showed that NAFLD induces liver-specific cytochrome P-450 (CYP)2E1-mediated metabolic oxidative stress after administration of the CYP2E1 substrate bromodichloromethane (BDCM) (Seth RK, Das S, Kumar A, Chanda A, Kadiiska MB, Michelotti G, Manautou J, Diehl AM, Chatterjee S. Toxicol Appl Pharmacol 274: 42-54, 2014; Seth RK, Kumar A, Das S, Kadiiska MB, Michelotti G, Diehl AM, Chatterjee S...
January 1, 2016: American Journal of Physiology. Renal Physiology
Wei Yang, Balachandra Gorentla, Xiao-Ping Zhong, Jinwook Shin
Invariant NKT (iNKT) cells, which express the invariant Vα14Jα18 TCR that recognizes lipid antigens, have the ability to rapidly respond to agonist stimulation, producing a variety of cytokines that can shape both innate and adaptive immunity. iNKT cells have been implicated in host defense against microbial infection, in anti-tumor immunity, and a multitude of diseases such as allergies, asthma, graft versus host disease, and obesity. Emerging evidence has demonstrated crucial role for mammalian target of rapamycin (mTOR) in immune cells, including iNKT...
December 2015: Molecular Immunology
Steven Bozinovski, Huei Jiunn Seow, Sheau Pyng Jamie Chan, Desiree Anthony, Jonathan McQualter, Michelle Hansen, Brendan J Jenkins, Gary P Anderson, Ross Vlahos
Cigarette smoke (CS) is the major cause of chronic obstructive pulmonary disease (COPD). Interleukin-17A (IL-17A) is a pivotal cytokine that regulates lung immunity and inflammation. The aim of the present study was to investigate how IL-17A regulates CS-induced lung inflammation in vivo. IL-17A knockout (KO) mice and neutralization of IL-17A in wild-type (WT) mice reduced macrophage and neutrophil recruitment and chemokine (C-C motif) ligand 2 (CCL2), CCL3 and matrix metalloproteinase (MMP)-12 mRNA expression in response to acute CS exposure...
November 2015: Clinical Science (1979-)
Hai-Ping Wang, Zhi-Gao He
Non-obese diabetes (NOD) mice are widely used as an animal model in studies of type I diabetes (TID). Treatment with complete Freund's adjuvant (CFA) in pro-diabetic NOD mice is known to inhibit disease progression by activating CD1d-specific natural killer (NK) T cells and inducing interleukin (IL)-17 secretion in innate immune cells. The aim of the present study was to examine the effect of incomplete Freund's adjuvant (IFA) and L. monocytogenes treatment on the development of TID in NOD mice. This combined treatment of IFA and L...
May 2015: Experimental and Therapeutic Medicine
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