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https://www.readbyqxmd.com/read/29449556/cd1d-dependent-immune-suppression-mediated-by-regulatory-b-cells-through-modulations-of-inkt-cells
#1
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
https://www.readbyqxmd.com/read/29434853/intracellular-il-4-and-ifn-%C3%AE-expression-in-inkt-cells-from-patients-with-chronic-lymphocytic-leukemia
#2
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
https://www.readbyqxmd.com/read/29419749/deficiency-of-invariant-natural-killer-t-cells-does-not-protect-against-obesity-but-exacerbates-atherosclerosis-in-ldlr-mice
#3
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
https://www.readbyqxmd.com/read/29406905/autoimmunity-in-multiple-sclerosis-role-of-sphingolipids-invariant-nkt-cells-and-other-immune-elements-in-control-of-inflammation-and-neurodegeneration
#4
REVIEW
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
https://www.readbyqxmd.com/read/29389901/the-janus-face-of-nkt-cell-function-in-autoimmunity-and-infectious-diseases
#5
REVIEW
Alessandra Torina, Giuliana Guggino, Marco Pio La Manna, Guido Sireci
Natural killer T cells (NKT) are a subset of T lymphocytes bridging innate and adaptive immunity. These cells recognize self and microbial glycolipids bound to non-polymorphic and highly conserved CD1d molecules. Three NKT cell subsets, type I, II, and NKT-like expressing different antigen receptors (TCR) were described and TCR activation promotes intracellular events leading to specific functional activities. NKT can exhibit different functions depending on the secretion of soluble molecules and the interaction with other cell types...
February 1, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29378774/cd1d-mediated-lipid-presentation-by-cd11c-cells-regulates-intestinal-homeostasis
#6
Julia Sáez de Guinoa, Rebeca Jimeno, Mauro Gaya, David Kipling, María José Garzón, Deborah Dunn-Walters, Carles Ubeda, Patricia Barral
Intestinal homeostasis relies on a continuous dialogue between the commensal bacteria and the immune system. Natural killer T (NKT) cells, which recognize CD1d-restricted microbial lipids and self-lipids, contribute to the regulation of mucosal immunity, yet the mechanisms underlying their functions remain poorly understood. Here, we demonstrate that NKT cells respond to intestinal lipids and CD11c+ cells (including dendritic cells (DCs) and macrophages) are essential to mediate lipid presentation within the gut ultimately controlling intestinal NKT cell homeostasis and activation...
January 29, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29363849/impact-of-th1-th2-cytokine-polarity-induced-by-invariant-nkt-cells-on-the-incidence-of-pregnancy-loss-in-mice
#7
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
https://www.readbyqxmd.com/read/29363187/gpr65-inhibits-experimental-autoimmune-encephalomyelitis-through-cd4-t-cell-independent-mechanisms-that-include-effects-on-inkt-cells
#8
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
https://www.readbyqxmd.com/read/29351991/differing-roles-of-cd1d2-and-cd1d1-proteins-in-type-i-natural-killer-t-cell-development-and-function
#9
Srinivasan Sundararaj, Jingjing Zhang, S Harsha Krovi, Romain Bedel, Kathryn D Tuttle, Natacha Veerapen, Gurdyal S Besra, Yogesh Khandokar, T Praveena, Jérôme Le Nours, Jennifer L Matsuda, Jamie Rossjohn, Laurent Gapin
MHC class I-like CD1 molecules have evolved to present lipid-based antigens to T cells. Differences in the antigen-binding clefts of the CD1 family members determine the conformation and size of the lipids that are presented, although the factors that shape CD1 diversity remain unclear. In mice, two homologous genes, CD1D1 and CD1D2, encode the CD1d protein, which is essential to the development and function of natural killer T (NKT) cells. However, it remains unclear whether both CD1d isoforms are equivalent in their antigen presentation capacity and functions...
January 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29349658/the-il-10-producing-regulatory-b-cells-b10-cells-and-regulatory-t-cell-subsets-in-neuromyelitis-optica-spectrum-disorder
#10
Eun Bin Cho, Hye-Jin Cho, Jin Myoung Seok, Ju-Hong Min, Eun-Suk Kang, Byoung Joon Kim
B cells contribute to the pathogenesis of neuromyelitis optica (NMO) by producing Aquaporin 4-specific autoantibodies (AQP4-ab); on the other hand, there are certain B cells that suppress immune responses by producing regulatory cytokines, such as IL-10. In this study, we investigated the presence of IL-10-producing Breg cells among lymphocyte subsets. Twenty-two seropositive NMO spectrum disorder (NMOSD) patients (29 samples) and 13 healthy controls (HCs) (14 samples) were enrolled. All NMOSD patients have received one or more immunosuppressive drugs...
January 19, 2018: Neurological Sciences
https://www.readbyqxmd.com/read/29346401/cd1d-deficiency-inhibits-the-development-of-abdominal-aortic-aneurysms-in-ldl-receptor-deficient-mice
#11
Gijs H M van Puijvelde, Amanda C Foks, Rosemarie E van Bochove, Ilze Bot, Kim L L Habets, Saskia C de Jager, Mariëtte N D Ter Borg, Puck van Osch, Louis Boon, Mariska Vos, Vivian de Waard, Johan Kuiper
An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta leading to serious complications and mostly to death. AAA development is associated with an accumulation of inflammatory cells in the aorta including NKT cells. An important factor in promoting the recruitment of these inflammatory cells into tissues and thereby contributing to the development of AAA is angiotensin II (Ang II). We demonstrate that a deficiency in CD1d dependent NKT cells under hyperlipidemic conditions (LDLr-/-CD1d-/- mice) results in a strong decline in the severity of angiotensin II induced aneurysm formation when compared with LDLr-/- mice...
2018: PloS One
https://www.readbyqxmd.com/read/29302250/lineage-differentiation-program-of-invariant-natural-killer-t-cells
#12
REVIEW
Dong-Il Kwon, You Jeong Lee
Invariant natural killer T (iNKT) cells are innate T cells restricted by CD1d molecules. They are positively selected in the thymic cortex and migrate to the medullary area, in which they differentiate into 3 different lineages. Promyelocytic leukemia zinc finger (PLZF) modulates this process, and PLZFhigh, PLZFintermediate, and PLZFlow iNKT cells are designated as NKT2, NKT17, and NKT1 cells, respectively. Analogous to conventional helper CD4 T cells, each subset expresses distinct combinations of transcription factors and produces different cytokines...
December 2017: Immune Network
https://www.readbyqxmd.com/read/29280974/harnessing-invariant-nkt-cells-to-improve-influenza-vaccines-a-pig-perspective
#13
REVIEW
Guan Yang, Jürgen A Richt, John P Driver
Invariant natural killer T (iNKT) cells are an "innate-like" T cell lineage that recognize glycolipid rather than peptide antigens by their semi-invariant T cell receptors. Because iNKT cells can stimulate an extensive array of immune responses, there is considerable interest in targeting these cells to enhance human vaccines against a wide range of microbial pathogens. However, long overlooked is the potential to harness iNKT cell antigens as vaccine adjuvants for domestic animal species that express the iNKT cell-CD1d system...
December 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29191573/excessive-interferon-%C3%AE-signaling-in-autoimmunity-alters-glycosphingolipid-processing-in-b-cells
#14
Andy Hee-Meng Tan, Arleen Sanny, Sze-Wai Ng, Ying-Swan Ho, Nurhidayah Basri, Alison Ping Lee, Kong-Peng Lam
Excessive interferon-α (IFN-α) production by innate immune cells is a hallmark of autoimmune diseases. What other cell type secretes IFN-α and how IFN-α affects immune cell metabolism and homeostasis in autoimmunity are largely unclear. Here, we report that autoimmune B cells, arising from two different B cell-specific genetic lesions in mice, secrete IFN-α. In addition, IFN-α, found in abundance in autoimmunity, elicited profound changes in the B cell lipidome, increasing their expression of glycosphingolipids (GSLs) and leading to their CD1d-mediated depletion of iNKT cells in vitro and in vivo...
November 27, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29183709/unappreciated-diversity-within-the-pool-of-cd1d-restricted-t-cells
#15
REVIEW
Daniel G Pellicci, Adam P Uldrich
Studies of lipid reactive CD1d-restricted T cells have focussed on α-galactosylceramide reactive semi-invariant Type I NKT cells, which influence a broad range of immune responses. Much less is known about other CD1d-restricted T cells with respect to TCR diversity, function, the types of antigens they recognize and how they specifically recognize antigens presented by CD1d. In this review, we reflect on recent literature that highlights unexpected complexity within the pool of CD1d-restricted T cells and emphasize how TCR diversity greatly broadens the scope of antigen recognition...
November 25, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29182669/nkt-cells-contribute-to-basal-il-4-production-but-are-not-required-to-induce-experimental-asthma
#16
Christopher G McKnight, Suzanne C Morris, Charles Perkins, Zhenqi Zhu, David A Hildeman, Albert Bendelac, Fred D Finkelman
CD1d-deficiency results in a selective deletion of NKT cells in mice that is reported to prevent murine allergic airway disease (AAD). Because we find 2-3 fold lower basal IL-4 production in CD1d- mice than in wild-type (WT) mice, we hypothesized that the contribution made by NKT cells to AAD would depend on the strength of the stimulus used to induce the disease. Consequently, we compared CD1d-deficient mice to WT mice in the development of AAD, using several models of disease induction that differed in the type and dose of allergen, the site of sensitization and the duration of immunization...
2017: PloS One
https://www.readbyqxmd.com/read/29179729/deficiency-of-innate-like-t-lymphocytes-in-chronic-obstructive-pulmonary-disease
#17
Mariann Szabó, Veronika Sárosi, Zoltán Balikó, Kornélia Bodó, Nelli Farkas, Tímea Berki, Péter Engelmann
BACKGROUND: Based on the phenotypic and functional characteristics unconventional T-lymphocytes such as invariant natural killer T (iNKT) cells and mucosal-associated invariant T (MAIT) cells link the innate and adaptive immune responses. Up to now data are scarce about their involvement in pulmonary disorders including chronic obstructive pulmonary disease (COPD). This study explores simultaneously the frequencies of iNKT and MAIT cells in the peripheral blood and sputum of stable and exacerbating COPD patients...
November 28, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29163518/mixed-signals-co-stimulation-in-invariant-natural-killer-t-cell-mediated-cancer-immunotherapy
#18
REVIEW
Susannah C Shissler, Michael S Lee, Tonya J Webb
Invariant natural killer T (iNKT) cells are an integral component of the immune system and play an important role in antitumor immunity. Upon activation, iNKT cells can directly kill malignant cells as well as rapidly produce cytokines that stimulate other immune cells, making them a front line defense against tumorigenesis. Unfortunately, iNKT cell number and activity are reduced in multiple cancer types. This anergy is often associated with upregulation of co-inhibitory markers such as programmed death-1...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163493/alpha-galactosylceramide-cd1d-antibody-fusion-proteins-redirect-invariant-natural-killer-t-cell-immunity-to-solid-tumors-and-promote-prolonged-therapeutic-responses
#19
REVIEW
Lianjun Zhang, Alena Donda
Major progress in cancer immunotherapies have been obtained by the use of tumor targeting strategies, in particular with the development of bi-functional fusion proteins such as ImmTacs or BiTes, which engage effector T cells for targeted elimination of tumor cells. Given the significance of invariant natural killer T (iNKT) cells in bridging innate and adaptive immunity, we have developed a bi-functional protein composed of the extracellular part of CD1d molecule that was genetically fused to an scFv fragment from high affinity antibodies against HER2 or CEA...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29152605/hepatic-natural-killer-t-cell-and-cd8-t-cell-signatures-in-mice-with-nonalcoholic-steatohepatitis
#20
Jashdeep Bhattacharjee, Michelle Kirby, Samir Softic, Lili Miles, Rosa-Maria Salazar-Gonzalez, Pranav Shivakumar, Rohit Kohli
Hepatic inflammation is a key pathological feature of Nonalcoholic Steatohepatitis (NASH). Natural Killer T-cells (NKT) and CD8+ T-cells are known to play an important role in obesity related adipose tissue inflammation. We hypothesized that these same inflammatory phenotypes would be present in progressive NASH. We used a previously established high fat high carbohydrate (HFHC) murine obesogenic diet model of progressive NASH to investigate the role of NKT cells and CD8+ T-cells in C57Bl6/J mice. Further, to better understand the impact of these cell populations; CD1d-deficient and CD8+ T-cell depleted mice were subjected to HFHC diet for 16 weeks...
June 2017: Hepatology Communications
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