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Filippo Cortesi, Gloria Delfanti, Andrea Grilli, Arianna Calcinotto, Francesca Gorini, Ferdinando Pucci, Roberta Lucianò, Matteo Grioni, Alessandra Recchia, Fabio Benigni, Alberto Briganti, Andrea Salonia, Michele De Palma, Silvio Bicciato, Claudio Doglioni, Matteo Bellone, Giulia Casorati, Paolo Dellabona
Heterotypic cellular and molecular interactions in the tumor microenvironment (TME) control cancer progression. Here, we show that CD1d-restricted invariant natural killer (iNKT) cells control prostate cancer (PCa) progression by sculpting the TME. In a mouse PCa model, iNKT cells restrained the pro-angiogenic and immunosuppressive capabilities of tumor-infiltrating immune cells by reducing pro-angiogenic TIE2+ , M2-like macrophages (TEMs), and sustaining pro-inflammatory M1-like macrophages. iNKT cells directly contacted macrophages in the PCa stroma, and iNKT cell transfer into tumor-bearing mice abated TEMs, delaying tumor progression...
March 13, 2018: Cell Reports
Yasuyuki Negishi, Tomoko Ichikawa, Toshiyuki Takeshita, Hidemi Takahashi
Unexpected fetal loss is one of the common complications of pregnancy; however, the pathogenesis of many miscarriages, particularly those not associated with infections, is unknown. We previously found that activated DEC-205+ dendritic cells (DCs) and NK1.1+ invariant natural killer T (iNKT) cells are recruited into the myometrium of mice when miscarriage is induced by the intraperitoneal administration of α-galactosylceramide (α-GalCer). Here we demonstrate that the adoptive transfer of DEC-205+ bone marrow-derived DCs cocultured with α-GalCer (DEC-205+ BMDCs-c/w-α-GalCer) directly induced marked fetal loss by syngeneic pregnant C57BL/6 (B6) mice and allogeneic mice (B6 (♀) × BALB/c (♂)), which was accompanied by the accumulation of activated iNKT cells in the myometrium...
March 9, 2018: European Journal of Immunology
Jin Young Huh, Yoon Jeong Park, Jae Bum Kim
Obesity-induced adipose tissue inflammation is regulated by various immune cells for innate and adaptive immunity. Among adipose tissue immune cells, it has been proposed that invariant Natural Killer T (iNKT) cells play crucial roles in anti-inflammatory responses in obesity. iNKT cells recognize 'lipid' antigens loaded on CD1d of antigen presenting cells and modulate immune responses by secreting Th1 or Th2 type cytokines depending on species of lipid antigens, antigen presenting cell types, and environmental cytokine milieu...
March 6, 2018: Adipocyte
Xijun Ou, Jianxin Huo, Yuhan Huang, Yan-Feng Li, Shengli Xu, Kong-Peng Lam
Invariant natural killer T (iNKT) cells develop from CD4+ CD8+ double-positive (DP) thymocytes and express an invariant Vα 14-Jα 18 T-cell receptor (TCR) α-chain. Generation of these cells requires the prolonged survival of DP thymocytes to allow for Vα 14-Jα 18 gene rearrangements and strong TCR signaling to induce the expression of the iNKT lineage-specific transcription factor PLZF. Here, we report that the transcription factor Yin Yang 1 (YY1) is essential for iNKT cell formation. Thymocytes lacking YY1 displayed a block in iNKT cell development at the earliest progenitor stage...
March 2, 2018: Cellular & Molecular Immunology
Anthony J St Leger, Anna M Hansen, Hatice Karauzum, Reiko Horai, Cheng-Rong Yu, Arian Laurence, Katrin D Mayer-Barber, Phyllis Silver, Rafael Villasmil, Charles Egwuagu, Sandip K Datta, Rachel R Caspi
Appropriate regulation of IL-17 production in the host can mean the difference between effective control of pathogens and uncontrolled inflammation that causes tissue damage. Investigation of conventional CD4+ T cells (Th17 cells) has yielded invaluable insights into IL-17 function and its regulation. More recently, we and others reported production of IL-17 from innate αβ+ T cell populations, which was shown to occur primarily via IL-23R signaling through the transcription factor STAT-3. In our current study, we identify promyelocytic leukemia zinc finger (PLZF)-expressing iNKT, CD4- /CD8+ , and CD4- /CD8- (DN) αβ+T cells, which produce IL-17 in response to TCR and IL-1 receptor ligation independently of STAT-3 signaling...
February 28, 2018: Journal of Experimental Medicine
Hong Yan, Zhao Xiangyu, Yu Xingxing, Bian Zhilei, Chang Yingjun, Yu Wang, Zhang Xiaohui, Xu Lanping, Huang Xiaojun, Zhao Xiaosu
INTRODUCTION: Invariant natural killer T cells (iNKTs) are a rare but vital subset of immunomodulatory T cells and play an important role in allogeneic hematopoietic stem cell trans-plantation (HSCT). The association of donor characteristics with the number and frequency of the iNKTs subsets in allografts remains poorly understood. In this paper, we prospectively investigate the association of donor characteristics with iNKTs dose and frequency in granulocyte-colony-stimulating factor (G-CSF) mobilized marrow and peripheral blood harvests...
February 20, 2018: Transplant Immunology
Yeon Duk Woo, Jaemoon Koh, Hye-Ryun Kang, Hye Young Kim, Doo Hyun Chung
BACKGROUND: The XCL1-XCR1 axis has been reported to play a role in immune homeostasis and inflammation. However, it is not known whether this axis has a critical function in allergic asthma. OBJECTIVE: In the present study, we explored that the iNKT cell-mediated XCL1-XCR1 axis regulated the allergic asthma. METHODS: Ovalbumin (OVA) or house dust mite (HDM)-induced asthma was developed in XCL1 or XCR1 knockout (KO) mice. RESULTS: XCL1 or XCR1 KO mice showed attenuation in airway hyperresponsiveness (AHR), numbers of CD103+ dendritic cells (DCs), and Th2 responses in the lungs compared with wild-type (WT) mice during OVA or HDM-induced asthma...
February 20, 2018: Journal of Allergy and Clinical Immunology
Fengjuan Jiang, Hui Liu, Zhaoyun Liu, Siyang Yan, Jin Chen, Qing Shao, Lijuan Li, Jia Song, Guojin Wang, Zonghong Shao, Rong Fu
Recent research showed that invariant natural killer T (iNKT) cells take part in the regulation of osteoclastogenesis. While the role of iNKT cells in myeloma bone disease (MBD) remains unclear. In our study, the quantity of iNKT cells and the levels of cytokines produced by them were measured by flow cytometry. iNKT cells and osteoclasts were induced from peripheral blood mononuclear cells after activation by α-GalCer or RANKL in vitro. Then, gene expressions and the levels of cytokines were determined by RT-PCR and ELISA, respectively...
February 23, 2018: Journal of Cellular and Molecular Medicine
Claudia Burrello, Federica Garavaglia, Fulvia Milena Cribiù, Giulia Ercoli, Silvano Bosari, Flavio Caprioli, Federica Facciotti
The gut mucosa is continuously exposed to a vast community of microorganisms, collectively defined as microbiota, establishing a mutualistic relationship with the host and contributing to shape the immune system. Gut microbiota is acquired at birth, and its composition is relatively stable during the entire adult life. Intestinal dysbiosis, defined as a microbial imbalance of gut bacterial communities, can be caused by several factors, including bacterial infections and antibiotic use, and has been associated with an increased risk to develop or exacerbate immune-mediated pathologies, such as allergic reactions, asthma, and inflammatory bowel diseases...
2018: Frontiers in Medicine
Mihalis Verykokakis, Barbara L Kee
Invariant Natural Killer T (iNKT) cells are a heterogeneous innate T cell population that recognizes lipid antigens. Despite the monospecific nature of their T cell receptor, iNKT cells differentiate into stable sublineages during thymic development, before foreign antigen encounter. How iNKT cell subsets acquire and maintain their functional programs is a central question in innate lymphocyte biology. Global transcriptional and epigenetic profiling of iNKT subsets has provided insights into the internal wiring of these subsets that defines their identity...
February 13, 2018: Current Opinion in Immunology
K Oleinika, E C Rosser, D E Matei, K Nistala, A Bosma, I Drozdov, C Mauri
Regulatory B cells (Breg) express high levels of CD1d that presents lipid antigens to invariant natural killer T (iNKT) cells. The function of CD1d in Breg biology and iNKT cell activity during inflammation remains unclear. Here we show, using chimeric mice, cell depletion and adoptive cell transfer, that CD1d-lipid presentation by Bregs induces iNKT cells to secrete interferon (IFN)-γ to contribute, partially, to the downregulation of T helper (Th)1 and Th17-adaptive immune responses and ameliorate experimental arthritis...
February 15, 2018: Nature Communications
Agnieszka Bojarska-Junak, Małgorzata Waldowska, Justyna Woś, Sylwia Chocholska, Iwona Hus, Waldemar Tomczak, Michał Dzik, Marek Hus, Jacek Roliński
Malignant B cells in chronic lymphocytic leukemia serve an essential role in the whole immune response, so their interactions with other immune cells are more complex than observed in solid tumors. The latest study results indicate that the immune dysregulation in chronic lymphocytic leukemia (CLL) also affects a small population of invariant natural killer T cells (iNKT). Using peripheral blood iNKT cells obtained from patients with CLL, the objective of the present study was to assess the intracellular expression of typical cytokines involved in the Th1 (IFN-γ) and Th2 (IL-4) response pathways following stimulation with the iNKT-specific ligand α-galactosylceramide...
February 2018: Oncology Letters
Shilpi Chandra, Gerhard Wingender, Jason A Greenbaum, Archana Khurana, Amin M Gholami, Anusha-Preethi Ganesan, Michael Rosenbach, Katy Jaffee, James E Gern, Robert Wood, George O'Connor, Megan Sandel, Meyer Kattan, Leonard Bacharier, Alkis Togias, Anthony A Horner, Mitchell Kronenberg
Humans have populations of innate-like T lymphocytes with an invariant TCR α-chain that recognize nonpeptide Ags, including invariant NKT (iNKT) cells and mucosal-associated invariant T (MAIT) cells. iNKT cell involvement in human asthma is controversial, whereas there has been little analysis of MAIT cells. Using peripheral blood cells from 110 participants from the Urban Environment and Childhood Asthma (URECA) birth cohort study, these cells were analyzed for number and function. We determined whether iNKT cell or MAIT cell frequency at 1 y is correlated with the cytokine polarization of mainstream CD4+ T cells and/or the development of asthma by age 7 y...
February 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Savitha Subramanian, Leela Goodspeed, Shari Wang, Yilei Ding, Kevin D O'Brien, Godfrey S Getz, Alan Chait, Catherine A Reardon
Obesity is a chronic inflammatory state characterized by altered levels of adipose tissue immune cell populations. Natural killer T (NKT) cells are CD1d restricted lymphocyte subsets that recognize lipid antigens whose level decreases in obese adipose tissue. However, studies in mice with deficiency or increased levels of NKT cells have yielded contradictory results, so the exact role of these cells in obesity and adipose tissue inflammation is not yet established. We previously showed that Ldlr-/- mice with excess invariant NKT (iNKT) cells demonstrate significant weight gain, adiposity, metabolic abnormalities, and atherosclerosis...
February 8, 2018: International Journal of Molecular Sciences
Sumedha Roy, Amanda J Moore, Cassandra Love, Anupama Reddy, Deepthi Rajagopalan, Sandeep S Dave, Leping Li, Cornelis Murre, Yuan Zhuang
A family of transcription factors known as E proteins, and their antagonists, Id proteins, regulate T cell differentiation at critical developmental checkpoints. Id proteins promote the differentiation of conventional αβ T cells and suppress the expansion of innate-like αβ T cells known as invariant natural killer T (iNKT) cells. However, it remains to be determined whether Id proteins differentially regulate these distinct lineage choices in early stages of T cell development. In this manuscript, we report that in Id-deficient mice, uninhibited activity of the E protein family member E2A mediates activation of genes that support iNKT cell development and function...
2018: Frontiers in Immunology
Maria Podbielska, Joan O'Keeffe, Edward L Hogan
Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. It is classified as being an autoimmune response in the genetically susceptible individual to a persistent but unidentified antigen(s). Both the adaptive and the innate immune systems are likely to contribute significantly to MS pathogenesis. This review summarizes current understanding of the characteristics of MS autoimmunity in the initiation and progression of the disease. In particular we find it timely to classify the autoimmune responses by focusing on the immunogenic features of myelin-derived lipids in MS including molecular mimicry; on alterations of bioactive sphingolipids mediators in MS; and on functional roles for regulatory effector cells, including innate lymphocyte populations, like the invariant NKT (iNKT) cells which bridge adaptive and innate immune systems...
February 15, 2018: Journal of the Neurological Sciences
Meng Wang, Cynthia Ju
No abstract text is available yet for this article.
February 5, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Mari Hoya, Takeshi Nagamatsu, Tatsuya Fujii, Danny J Schust, Hiroko Oda, Naoya Akiba, Takayuki Iriyama, Kei Kawana, Yutaka Osuga, Tomoyuki Fujii
OBJECTIVE: This study aimed to investigate the association of Th1/Th2 polarity induced by CD1d-restricted invariant natural killer T (iNKT) cells with pregnancy outcome. METHODS: Two types of iNKT cell stimulants with different cytokine induction properties, alpha-galactosylceramide (AGC; Th1-biased inducer), and a sphingosine-truncated derivative of AGC (OCH; Th2-biased inducer) were administered to pregnant mice on day 9.5 post-coitus (pc), and the incidence of pregnancy loss was evaluated...
January 24, 2018: American Journal of Reproductive Immunology: AJRI
Rushika C Wirasinha, Dipti Vijayan, Nicola J Smith, Grant P Parnell, Alexander Swarbrick, Robert Brink, Cecile King, Graeme Stewart, David R Booth, Marcel Batten
The G protein-coupled receptor 65 (GPR65) gene has been genetically associated with several autoimmune diseases, including multiple sclerosis (MS). GPR65 is predominantly expressed in lymphoid organs and is activated by extracellular protons. In this study, we tested whether GPR65 plays a functional role in demyelinating autoimmune disease. Using a murine model of MS, experimental autoimmune encephalomyelitis (EAE), we found that Gpr65-deficient mice develop exacerbated disease. CD4+ helper T cells are key drivers of EAE pathogenesis, however, Gpr65 deficiency in these cells did not contribute to the observed exacerbated disease...
December 19, 2017: Immunology and Cell Biology
Dongjin Jeong, Hye Young Kim, Doo Hyun Chung
Invariant NKT (iNKT) cells are a distinct subset of T cells that exert Janus-like functions in vivo by producing IFN-γ and IL-4. Sodium chloride modulates the functions of various immune cells, including conventional CD4+ T cells and macrophages. However, it is not known whether sodium chloride affects iNKT cell function, so we addressed this issue. Sodium chloride inhibited IFN-γ, but not IL-4, production by iNKT cells upon TCR or TCR-independent (IL-12 and IL-18) stimulation in a dose-dependent manner. Consistently, sodium chloride reduced the expression level of tbx21, but not gata-3, in iNKT cells stimulated with TCR engagement or IL-12 + IL-18...
January 2018: Journal of Leukocyte Biology
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