galactosylceramides

Summary

Summary: Cerebrosides which contain as their polar head group a galactose moiety bound in glycosidic linkage to the hydroxyl group of ceramide. Their accumulation in tissue, due to a defect in beta-galactosidase, is the cause of galactosylceramide lipidosis or globoid cell leukodystrophy.

Top Publications

  1. Nicol A, Tazbirkova A, Nieda M. Comparison of clinical and immunological effects of intravenous and intradermal administration of ?-galactosylceramide (KRN7000)-pulsed dendritic cells. Clin Cancer Res. 2011;17:5140-51 pubmed publisher
    ..We conclude that therapy with ?-GalCer-pulsed DC induced clinically beneficial immune responses that are highly dependent on cell dose and administration route. ..
  2. Velazquez P, Cameron T, Kinjo Y, Nagarajan N, Kronenberg M, Dustin M. Cutting edge: activation by innate cytokines or microbial antigens can cause arrest of natural killer T cell patrolling of liver sinusoids. J Immunol. 2008;180:2024-8 pubmed
    ..Interestingly, NKT cell arrest also results from IL-12 and IL-18 synergistic activation. Thus, innate cytokines and natural microbial TCR agonists trigger sinusoidal NKT cell arrest and an effector response. ..
  3. Liu Z, Bittman R. Synthesis of C-glycoside analogues of ?-galactosylceramide via linear allylic C-H oxidation and allyl cyanate to isocyanate rearrangement. Org Lett. 2012;14:620-3 pubmed publisher
    ..The key transformations include C-H oxidation, Sharpless asymmetric epoxidation, olefin cross metathesis, and an allyl cyanate to isocyanate rearrangement. ..
  4. Cerundolo V, Barral P, Batista F. Synthetic iNKT cell-agonists as vaccine adjuvants--finding the balance. Curr Opin Immunol. 2010;22:417-24 pubmed publisher
    ..In this article we explore strategies being investigated as means of increasing the specificity of and controlling the magnitude of the immune response generated by activation of iNKT cells with synthetic agonists. ..
  5. Yamasaki K, Horiguchi S, Kurosaki M, Kunii N, Nagato K, Hanaoka H, et al. Induction of NKT cell-specific immune responses in cancer tissues after NKT cell-targeted adoptive immunotherapy. Clin Immunol. 2011;138:255-65 pubmed publisher
    ..The combination therapy induced NKT cell-specific immune responses in cancer tissues that were associated with beneficial clinical effects. ..
  6. Bricard G, Venkataswamy M, Yu K, Im J, Ndonye R, Howell A, et al. ?-galactosylceramide analogs with weak agonist activity for human iNKT cells define new candidate anti-inflammatory agents. PLoS ONE. 2010;5:e14374 pubmed publisher
  7. Farokhi F, Grellier P, Clement M, Roussakis C, Loiseau P, Genin Seward E, et al. Antimalarial activity of axidjiferosides, new ?-galactosylceramides from the African sponge Axinyssa djiferi. Mar Drugs. 2013;11:1304-15 pubmed publisher
    ..Thus, it seems that galactosylceramides with a ? anomeric configuration may be suitable in searching for new antimalarial drugs.
  8. Taraban V, Martin S, Attfield K, Glennie M, Elliott T, Elewaut D, et al. Invariant NKT cells promote CD8+ cytotoxic T cell responses by inducing CD70 expression on dendritic cells. J Immunol. 2008;180:4615-20 pubmed
    ..These results define a key role for CD70 in linking the innate response of iNKT cells to the activation of CD8(+) T cells. ..
  9. Simoni Y, Diana J, Ghazarian L, Beaudoin L, Lehuen A. Therapeutic manipulation of natural killer (NK) T cells in autoimmunity: are we close to reality?. Clin Exp Immunol. 2013;171:8-19 pubmed publisher
    ..We also discuss the promise of NK T cell manipulations: restoration of function, specific activation, depletion and the relevance of these treatments to human autoimmune diseases. ..

More Information

Publications84

  1. Bai L, Constantinides M, Thomas S, Reboulet R, Meng F, Koentgen F, et al. Distinct APCs explain the cytokine bias of ?-galactosylceramide variants in vivo. J Immunol. 2012;188:3053-61 pubmed publisher
    ..Conversely, forced presentation of the Th2 variants by DC induced high IL-12. Thus, lipid structural variations that do not alter TCR recognition can activate distinct Th1 or Th2 cellular networks by changing APC targeting in vivo. ..
  2. Guillonneau C, Mintern J, Hubert F, Hurt A, Besra G, Porcelli S, et al. Combined NKT cell activation and influenza virus vaccination boosts memory CTL generation and protective immunity. Proc Natl Acad Sci U S A. 2009;106:3330-5 pubmed publisher
  3. Osterbye T, Funda D, Fundova P, Mansson J, Tlaskalova Hogenova H, Buschard K. A subset of human pancreatic beta cells express functional CD14 receptors: a signaling pathway for beta cell-related glycolipids, sulfatide and ?-galactosylceramide. Diabetes Metab Res Rev. 2010;26:656-67 pubmed publisher
    ..The CD14 expression on a subset of human beta-cells may play a role in the innate surveillance of the endocrine environment but may also contribute to innate immune mechanisms in the early stages of beta-cell aggression. ..
  4. Pellicci D, Clarke A, Patel O, Mallevaey T, Beddoe T, Le Nours J, et al. Recognition of ?-linked self glycolipids mediated by natural killer T cell antigen receptors. Nat Immunol. 2011;12:827-33 pubmed publisher
    ..Thus, the NKT cell TCR molds the ?-linked self ligands to resemble the conformation of foreign ?-linked ligands, which shows that induced-fit molecular mimicry can underpin the self-reactivity of NKT cell TCRs to ?-linked antigens. ..
  5. Liang P, Imamura M, Li X, Wu D, Fujio M, Guy R, et al. Quantitative microarray analysis of intact glycolipid-CD1d interaction and correlation with cell-based cytokine production. J Am Chem Soc. 2008;130:12348-54 pubmed publisher
  6. Venkataswamy M, Baena A, Goldberg M, Bricard G, Im J, Chan J, et al. Incorporation of NKT cell-activating glycolipids enhances immunogenicity and vaccine efficacy of Mycobacterium bovis bacillus Calmette-Guerin. J Immunol. 2009;183:1644-56 pubmed publisher
    ..Our findings raise the possibility of a simple modification of BCG that could yield a more effective vaccine for control of tuberculosis. ..
  7. Li Q, Ndonye R, Illarionov P, Yu K, Jerud E, Diaz K, et al. Rapid identification of immunostimulatory alpha-galactosylceramides using synthetic combinatorial libraries. J Comb Chem. 2007;9:1084-93 pubmed
    Two 60+-membered libraries of alpha-galactosylceramides have been prepared by reactions between activated ester resins and two core, fully deprotected galactosylated sphingoid bases...
  8. Lang G, Devera T, Lang M. Requirement for CD1d expression by B cells to stimulate NKT cell-enhanced antibody production. Blood. 2008;111:2158-62 pubmed
    ..Our data show that the mechanism by which NKT cells enhance humoral immune responses involves interaction with CD1d-expressing B cells. ..
  9. Parekh V, Lalani S, Kim S, Halder R, Azuma M, Yagita H, et al. PD-1/PD-L blockade prevents anergy induction and enhances the anti-tumor activities of glycolipid-activated invariant NKT cells. J Immunol. 2009;182:2816-26 pubmed publisher
    ..Collectively, our findings reveal a critical role for the PD-1/PD-L costimulatory pathway in the alphaGalCer-mediated induction of iNKT cell anergy that can be targeted for the development of immunotherapies. ..
  10. Stirnemann K, Romero J, Baldi L, Robert B, Cesson V, Besra G, et al. Sustained activation and tumor targeting of NKT cells using a CD1d-anti-HER2-scFv fusion protein induce antitumor effects in mice. J Clin Invest. 2008;118:994-1005 pubmed publisher
    ..Targeting iNKT cells to the tumor site thus may activate a combined innate and adaptive immune response that may prove to be effective in cancer immunotherapy. ..
  11. Reilly E, Thompson E, Aspeslagh S, Wands J, Elewaut D, Brossay L. Activated iNKT cells promote memory CD8+ T cell differentiation during viral infection. PLoS ONE. 2012;7:e37991 pubmed publisher
    ..Overall, our data suggest that iNKT cell activation by ?-GalCer promotes the development of long-term protective immunity through increased fitness of central memory CD8(+) T cells, as a consequence of reduced inflammation. ..
  12. Shiozaki M, Tashiro T, Koshino H, Nakagawa R, Inoue S, Shigeura T, et al. Synthesis and biological activity of ester and ether analogues of alpha-galactosylceramide (KRN7000). Carbohydr Res. 2010;345:1663-84 pubmed publisher
    ..Ester analogues 30a, 31a, and 61 showed activity for IFNgamma and IL-4 production of iNKT cells, while ether (31b) and 4-methoxy ester (76) analogues of alpha-galactosylceramide were not active for iNKT cells. ..
  13. Raju R, Castillo B, Richardson S, Thakur M, Severins R, Kronenberg M, et al. Synthesis and evaluation of 3''- and 4''-deoxy and -fluoro analogs of the immunostimulatory glycolipid, KRN7000. Bioorg Med Chem Lett. 2009;19:4122-5 pubmed publisher
    ..In two of the hybridomas, 1.2 and 2H4, all of the analogs were immunostimulatory, while in the 1.4 hybridoma only the 4''-fluoro analog led to the production of significant levels of IL-2...
  14. Pei B, VELA J, Zajonc D, Kronenberg M. Interplay between carbohydrate and lipid in recognition of glycolipid antigens by natural killer T cells. Ann N Y Acad Sci. 2012;1253:68-79 pubmed publisher
    ..In this review, we summarize progress on identifying the sources of microbe-derived glycolipid antigens recognized by NKT cells and the biochemical basis for their recognition. ..
  15. Arora P, Venkataswamy M, Baena A, Bricard G, Li Q, Veerapen N, et al. A rapid fluorescence-based assay for classification of iNKT cell activating glycolipids. J Am Chem Soc. 2011;133:5198-201 pubmed publisher
  16. Bai L, Sagiv Y, Liu Y, Freigang S, Yu K, Teyton L, et al. Lysosomal recycling terminates CD1d-mediated presentation of short and polyunsaturated variants of the NKT cell lipid antigen alphaGalCer. Proc Natl Acad Sci U S A. 2009;106:10254-9 pubmed publisher
    ..They also suggest that direct lipid displacement is a potent mechanism underlying highly dynamic lipid exchange reactions in the lysosomal compartment that shape the repertoire of lipids associated with CD1d. ..
  17. Veerapen N, Brigl M, Garg S, Cerundolo V, Cox L, Brenner M, et al. Synthesis and biological activity of alpha-galactosyl ceramide KRN7000 and galactosyl (alpha1-->2) galactosyl ceramide. Bioorg Med Chem Lett. 2009;19:4288-91 pubmed publisher
  18. Fujii S, Shimizu K, Hemmi H, Steinman R. Innate Valpha14(+) natural killer T cells mature dendritic cells, leading to strong adaptive immunity. Immunol Rev. 2007;220:183-98 pubmed
    ..These findings help explain tumor protection via alpha-GalCer and urge development of the DC-NKT axis to provide innate and adaptive immunity to human cancers. ..
  19. Fujii S, Motohashi S, Shimizu K, Nakayama T, Yoshiga Y, Taniguchi M. Adjuvant activity mediated by iNKT cells. Semin Immunol. 2010;22:97-102 pubmed publisher
    ..9 months. Sixty percent of the patients in this group survived for more than 2 years with only a primary treatment and without tumor progression and metastasis. ..
  20. Li X, Fujio M, Imamura M, Wu D, Vasan S, Wong C, et al. Design of a potent CD1d-binding NKT cell ligand as a vaccine adjuvant. Proc Natl Acad Sci U S A. 2010;107:13010-5 pubmed publisher
    ..Through this rigorous and iterative screening process, we have identified a lead candidate glycolipid, 7DW8-5, that exhibits a superior adjuvant effect than alpha-GalCer on HIV and malaria vaccines in mice. ..
  21. Chang W, Kim J, Kim Y, Kim Y, Lee J, Azuma M, et al. Cutting edge: Programmed death-1/programmed death ligand 1 interaction regulates the induction and maintenance of invariant NKT cell anergy. J Immunol. 2008;181:6707-10 pubmed
    ..Our findings suggest that the PD-1/PD-L1 interaction is essential for the induction and maintenance of iNKT cell anergy. ..
  22. Huang Y, Chen A, Li X, Chen Z, Zhang W, Song Y, et al. Enhancement of HIV DNA vaccine immunogenicity by the NKT cell ligand, alpha-galactosylceramide. Vaccine. 2008;26:1807-16 pubmed publisher
    ..Since both mice and humans share the CD1d molecule, this information may aid in designing more effective DNA vaccines and vaccine adjuvants against HIV-1. ..
  23. Li Y, Girardi E, Wang J, Yu E, Painter G, Kronenberg M, et al. The V?14 invariant natural killer T cell TCR forces microbial glycolipids and CD1d into a conserved binding mode. J Exp Med. 2010;207:2383-93 pubmed publisher
    ..We propose that the TCR of iNKT cells binds with a conserved footprint onto CD1d, regardless of the bound glycolipid antigen, and that for microbial antigens this unique binding mode requires TCR-initiated conformational changes. ..
  24. Wun K, Borg N, Kjer Nielsen L, Beddoe T, Koh R, Richardson S, et al. A minimal binding footprint on CD1d-glycolipid is a basis for selection of the unique human NKT TCR. J Exp Med. 2008;205:939-49 pubmed publisher
    ..Accordingly, although the structural footprint at the NKT TCR-CD1d-alpha-GalCer is small, the energetic footprint is smaller still, and reveals the minimal requirements for CD1d restriction. ..
  25. Wang Y, Hu X, Guo C, Zhang Q, Peng J, Zhang J, et al. Polarization of natural killer T cells towards an NKT2 subpopulation occurs after stimulation with alpha-galactosylceramide and rhG-CSF in aplastic anemia. Acta Haematol. 2008;119:178-86 pubmed publisher
    ..In summary, our results indicate that polarization of NKT cells towards the NKT2 subpopulation occurs after co-stimulation with alpha-galactosylceramide and rhG-CSF in AA. ..
  26. Eckhardt M. The role and metabolism of sulfatide in the nervous system. Mol Neurobiol. 2008;37:93-103 pubmed publisher
    ..This review summarizes recent studies on the physiological and pathophysiological role of sulfatide using transgenic mice deficient in its synthesis or degradation. ..
  27. Silk J, Salio M, Reddy B, Shepherd D, Gileadi U, Brown J, et al. Cutting edge: nonglycosidic CD1d lipid ligands activate human and murine invariant NKT cells. J Immunol. 2008;180:6452-6 pubmed
    ..The ability of these compounds to assist the priming of Ag-specific immune responses while minimizing iNKT cell-dependent DC lysis makes them attractive adjuvants for vaccination strategies...
  28. Liu Z, Byun H, Bittman R. Synthesis of immunostimulatory alpha-C-galactosylceramide glycolipids via Sonogashira coupling, asymmetric epoxidation, and trichloroacetimidate-mediated epoxide opening. Org Lett. 2010;12:2974-7 pubmed publisher
    ..The key transformations include Sonogashira coupling, Sharpless asymmetric epoxidation, and Et(2)AlCl-catalyzed cyclization of an epoxytrichloroacetimidate to generate protected dihydrooxazine 21. ..
  29. Brigl M, Tatituri R, Watts G, Bhowruth V, Leadbetter E, Barton N, et al. Innate and cytokine-driven signals, rather than microbial antigens, dominate in natural killer T cell activation during microbial infection. J Exp Med. 2011;208:1163-77 pubmed publisher
    ..The example of adaptive MHC-restricted T cells, studies using synthetic pharmacological ?-galactosylceramides, and the recent discovery of microbial iNKT cell ligands have all suggested that recognition of foreign ..
  30. Wingender G, Krebs P, Beutler B, Kronenberg M. Antigen-specific cytotoxicity by invariant NKT cells in vivo is CD95/CD178-dependent and is correlated with antigenic potency. J Immunol. 2010;185:2721-9 pubmed publisher
    ..Therefore, unlike NK cells, which rely mostly on perforin/granzyme-mediated mechanisms, the Ag-specific cytotoxicity of iNKT cells in vivo is largely restricted to the CD95/CD178 pathway. ..
  31. Jervis P, Cox L, Besra G. Synthesis of a versatile building block for the preparation of 6-N-derivatized ?-galactosyl ceramides: rapid access to biologically active glycolipids. J Org Chem. 2011;76:320-3 pubmed publisher
    ..Biologically active glycolipids 6 and 8 have been synthesized to illustrate the applicability of the approach. ..
  32. Seki S, Nakashima H, Nakashima M, Kinoshita M. Antitumor immunity produced by the liver Kupffer cells, NK cells, NKT cells, and CD8 CD122 T cells. Clin Dev Immunol. 2011;2011:868345 pubmed publisher
    ..are also discussed...
  33. Pellicci D, Patel O, Kjer Nielsen L, Pang S, Sullivan L, Kyparissoudis K, et al. Differential recognition of CD1d-alpha-galactosyl ceramide by the V beta 8.2 and V beta 7 semi-invariant NKT T cell receptors. Immunity. 2009;31:47-59 pubmed publisher
    ..2 and V beta 7 residues within the CDR2 beta loop in mediating contacts with CD1d. Collectively we provide a structural basis for the differential NKT TCR V beta usage in NKT cells. ..
  34. Wu D, Fujio M, Wong C. Glycolipids as immunostimulating agents. Bioorg Med Chem. 2008;16:1073-83 pubmed
    ..A combination of structure-activity relationship (SAR), crystallographic studies, and discovery of new 'natural' antigens has led to greater understanding of the structural requirements for optimal natural killer T-cell activation. ..
  35. Trappeniers M, Goormans S, Van Beneden K, Decruy T, Linclau B, Al Shamkhani A, et al. Synthesis and in vitro evaluation of alpha-GalCer epimers. ChemMedChem. 2008;3:1061-70 pubmed publisher
    ..In this context, we report the synthesis and in vitro evaluation of alpha-Gal-D-xylo-Cer and two alpha-Gal-L-lyxo-Cer analogues, one with the natural acyl chain, the other with a truncated chain. ..
  36. Leadbetter E, Brigl M, Illarionov P, Cohen N, Luteran M, Pillai S, et al. NK T cells provide lipid antigen-specific cognate help for B cells. Proc Natl Acad Sci U S A. 2008;105:8339-44 pubmed publisher
  37. Michieletti M, Bracci A, Compostella F, De Libero G, Mori L, Fallarini S, et al. Synthesis of alpha-galactosyl ceramide (KRN7000) and analogues thereof via a common precursor and their preliminary biological assessment. J Org Chem. 2008;73:9192-5 pubmed publisher
    ..The analogues are able to activate iNKT cells when presented by CD1d expressing cells. ..
  38. Sullivan B, Nagarajan N, Wingender G, Wang J, Scott I, Tsuji M, et al. Mechanisms for glycolipid antigen-driven cytokine polarization by Valpha14i NKT cells. J Immunol. 2010;184:141-53 pubmed publisher
    ..Therefore, we suggest that the pharmacokinetic properties of glycolipids are a major determinant of cytokine skewing, suggesting a pathway for designing therapeutic glycolipids for modulating invariant NKT cell responses. ..
  39. Ly D, Tohn R, Rubin B, Blumenfeld H, Besra G, Veerapen N, et al. An alpha-galactosylceramide C20:2 N-acyl variant enhances anti-inflammatory and regulatory T cell-independent responses that prevent type 1 diabetes. Clin Exp Immunol. 2010;160:185-98 pubmed publisher
    ..The enhanced anti-inflammatory properties of C20:2 relative to KRN7000 suggest that C20:2 should be evaluated further as a drug to induce iNK T cell-mediated protection from T1D in humans. ..
  40. Godfrey D, Rossjohn J. New ways to turn on NKT cells. J Exp Med. 2011;208:1121-5 pubmed publisher
  41. Iizuka A, Ikarashi Y, Yoshida M, Heike Y, Takeda K, Quinn G, et al. Interleukin (IL)-4 promotes T helper type 2-biased natural killer T (NKT) cell expansion, which is regulated by NKT cell-derived interferon-gamma and IL-4. Immunology. 2008;123:100-7 pubmed
    ..This finding suggests that effective expansion of NKT cells requires Th2-biased culture conditions. ..
  42. Im J, Kang T, Lee S, Kim C, Lee S, Venkataswamy M, et al. Alteration of the relative levels of iNKT cell subsets is associated with chronic mycobacterial infections. Clin Immunol. 2008;127:214-24 pubmed publisher
    ..tuberculosis infection. Taken together, these findings indicate that the selective reduction of circulating DN iNKT cells is associated with chronic infections caused by M. tuberculosis and M. leprae. ..
  43. Biburger M, Tiegs G. Activation-induced NKT cell hyporesponsiveness protects from alpha-galactosylceramide hepatitis and is independent of active transregulatory factors. J Leukoc Biol. 2008;84:264-79 pubmed publisher
    ..Conversely, approaches to render NKT cells hyporesponsive may constitute new therapeutic strategies for diseases, where aberrant NKT cell activation is causally involved. ..
  44. Matulis G, Sanderson J, Lissin N, Asparuhova M, Bommineni G, Schumperli D, et al. Innate-like control of human iNKT cell autoreactivity via the hypervariable CDR3beta loop. PLoS Biol. 2010;8:e1000402 pubmed publisher
    ..This mechanism is relatively independent of the bound CD1d ligand and thus forms the basis of an inherent, CDR3beta dependent functional hierarchy of human iNKT cells. ..
  45. Joyce S, Girardi E, Zajonc D. NKT cell ligand recognition logic: molecular basis for a synaptic duet and transmission of inflammatory effectors. J Immunol. 2011;187:1081-9 pubmed publisher
    ..This review summarizes our current understanding of CD1d-restricted ligand recognition by NKT cells and how these innate-like lymphocytes regulate inflammation. ..
  46. Ohtaki H, Ito H, Ando K, Ishikawa T, Saito K, Imawari M, et al. Valpha14 NKT cells activated by alpha-galactosylceramide augment lipopolysaccharide-induced nitric oxide production in mouse intra-hepatic lymphocytes. Biochem Biophys Res Commun. 2009;378:579-83 pubmed publisher
    ..The liver injury may be induced by LPS and NO under the condition where Valpha14 NKT cells were activated. ..
  47. Wennekes T, van den Berg R, Boot R, van der Marel G, Overkleeft H, Aerts J. Glycosphingolipids--nature, function, and pharmacological modulation. Angew Chem Int Ed Engl. 2009;48:8848-69 pubmed publisher
    ..Special attention is paid to the clinical relevance of compounds directed at interfering with the factors responsible for glycosphingolipid metabolism. ..
  48. Woltman A, ter Borg M, Binda R, Sprengers D, von Blomberg B, Scheper R, et al. Alpha-galactosylceramide in chronic hepatitis B infection: results from a randomized placebo-controlled Phase I/II trial. Antivir Ther. 2009;14:809-18 pubmed publisher
    ..alpha-GalCer was poorly tolerated and is unlikely to be suitable as an alternative monotherapy to the current treatment regimen. ..
  49. Ho L, Denney L, Luhn K, Teoh D, Clelland C, McMichael A. Activation of invariant NKT cells enhances the innate immune response and improves the disease course in influenza A virus infection. Eur J Immunol. 2008;38:1913-22 pubmed publisher
    ..We conclude that activation of iNKT cells enhances early innate immune response in the lungs and contribute to antiviral immunity and improved disease course in influenza A virus infection. ..
  50. Schneiders F, Scheper R, von Blomberg B, Woltman A, Janssen H, van den Eertwegh A, et al. Clinical experience with ?-galactosylceramide (KRN7000) in patients with advanced cancer and chronic hepatitis B/C infection. Clin Immunol. 2011;140:130-41 pubmed publisher
  51. Moreno M, Molling J, von Mensdorff Pouilly S, Verheijen R, von Blomberg B, van den Eertwegh A, et al. In vitro expanded human invariant natural killer T-cells promote functional activity of natural killer cells. Clin Immunol. 2008;129:145-54 pubmed publisher
    ..These results suggest that adoptive transfer of ex vivo expanded iNKT cells will enhance NK cell function and is expected to enhance the efficacy of cancer immunotherapy, particularly in combination with IL-21 and alpha-GC. ..
  52. Dhodapkar M, Richter J. Harnessing natural killer T (NKT) cells in human myeloma: progress and challenges. Clin Immunol. 2011;140:160-6 pubmed publisher
    ..These results have set the stage for ongoing studies combining NKT activation with immune-modulatory drugs. Lessons learnt from these studies may inform the optimal application of human NKT based therapies in other settings as well. ..
  53. Kim S, Lalani S, Parekh V, Vincent T, Wu L, Van Kaer L. Impact of bacteria on the phenotype, functions, and therapeutic activities of invariant NKT cells in mice. J Clin Invest. 2008;118:2301-15 pubmed publisher
    ..These findings may have important implications for the development of iNKT cell-based therapies. ..
  54. Velmourougane G, Raju R, Bricard G, Im J, Besra G, Porcelli S, et al. Synthesis and evaluation of an acyl-chain unsaturated analog of the Th2 biasing, immunostimulatory glycolipid, OCH. Bioorg Med Chem Lett. 2009;19:3386-8 pubmed publisher
    ..Two related alpha-GalCers, 3 and 4, with saturated acyl chains were prepared for comparison. ..
  55. Wu L, Gabriel C, Parekh V, van Kaer L. Invariant natural killer T cells: innate-like T cells with potent immunomodulatory activities. Tissue Antigens. 2009;73:535-45 pubmed publisher
    ..Although alpha-GalCer treatment in humans was shown to be safe in the short term, further studies are needed to develop safe and effective iNKT-cell-based therapies. ..
  56. Tonti E, Galli G, Malzone C, Abrignani S, Casorati G, Dellabona P. NKT-cell help to B lymphocytes can occur independently of cognate interaction. Blood. 2009;113:370-6 pubmed publisher
    ..Thus, the alphaGalCer-induced help recapitulates the function of classical adjuvants that stimulate the innate immune system to support adaptive immune responses. ..
  57. Cerundolo V, Silk J, Masri S, Salio M. Harnessing invariant NKT cells in vaccination strategies. Nat Rev Immunol. 2009;9:28-38 pubmed publisher
    ..In addition, we describe structural and kinetic analyses that assist in the design of optimal iNKT-cell agonists that could be used in the clinical setting as vaccine adjuvants. ..
  58. Motohashi S, Nagato K, Kunii N, Yamamoto H, Yamasaki K, Okita K, et al. A phase I-II study of alpha-galactosylceramide-pulsed IL-2/GM-CSF-cultured peripheral blood mononuclear cells in patients with advanced and recurrent non-small cell lung cancer. J Immunol. 2009;182:2492-501 pubmed publisher
    ..These results are encouraging and warrant further evaluation for survival benefit of this immunotherapy. ..
  59. Kunii N, Horiguchi S, Motohashi S, Yamamoto H, Ueno N, Yamamoto S, et al. Combination therapy of in vitro-expanded natural killer T cells and alpha-galactosylceramide-pulsed antigen-presenting cells in patients with recurrent head and neck carcinoma. Cancer Sci. 2009;100:1092-8 pubmed publisher
    ..The use of such therapeutic modalities may be helpful in the management of tumors and therefore needs to be explored in further detail. The clinical trial registration number was UMIN000000722. ..
  60. Chiba A, Cohen N, Brigl M, Brennan P, Besra G, Brenner M. Rapid and reliable generation of invariant natural killer T-cell lines in vitro. Immunology. 2009;128:324-33 pubmed publisher
    ..Given the desire to study primary iNKT cells for many purposes, these iNKT cell lines should provide an important tool for the study of iNKT cell subsets, antigen and TCR specificity, activation, inactivation and effector functions. ..
  61. King I, Amiel E, Tighe M, Mohrs K, Veerapen N, Besra G, et al. The mechanism of splenic invariant NKT cell activation dictates localization in vivo. J Immunol. 2013;191:572-82 pubmed publisher
    ..Collectively, these data provide new insight into how iNKT cells may serve as a natural adjuvant in facilitating adaptive immune responses, irrespective of their tissue localization. ..
  62. Tyznik A, Farber E, Girardi E, Birkholz A, Li Y, Chitale S, et al. Glycolipids that elicit IFN-?-biased responses from natural killer T cells. Chem Biol. 2011;18:1620-30 pubmed publisher
    ..We provide insights into the mechanism of IFN-?-inducing compounds, and because our compounds activate human NKT cells, they could have therapeutic utility. ..
  63. Wojno J, Jukes J, Ghadbane H, Shepherd D, Besra G, Cerundolo V, et al. Amide analogues of CD1d agonists modulate iNKT-cell-mediated cytokine production. ACS Chem Biol. 2012;7:847-55 pubmed publisher
  64. Broxmeyer H, Christopherson K, Hangoc G, Cooper S, Mantel C, Renukaradhya G, et al. CD1d expression on and regulation of murine hematopoietic stem and progenitor cells. Blood. 2012;119:5731-41 pubmed publisher
    ..Pretreatment of normal BM cells with CD1d Abs greatly enhanced their engraftment of HSCs. The results of the present study implicate CD1d in a previously unrecognized regulatory role of normal and stressed hematopoiesis. ..
  65. Wu T, Lin K, Chang Y, Huang J, Cheng J, Yu A, et al. Avidity of CD1d-ligand-receptor ternary complex contributes to T-helper 1 (Th1) polarization and anticancer efficacy. Proc Natl Acad Sci U S A. 2011;108:17275-80 pubmed publisher
    ..Thus, this study provides a key to the rational design of Th1 biased CD1d reactive glycolipids in the future. ..
  66. Banchet Cadeddu A, Henon E, Dauchez M, Renault J, Monneaux F, Haudrechy A. The stimulating adventure of KRN 7000. Org Biomol Chem. 2011;9:3080-104 pubmed publisher
  67. Monteiro M, Almeida C, Caridade M, Ribot J, Duarte J, Agua Doce A, et al. Identification of regulatory Foxp3+ invariant NKT cells induced by TGF-beta. J Immunol. 2010;185:2157-63 pubmed publisher
    ..Our data thus unveil an unexpected capacity of iNKT cells to acquire regulatory functions that may contribute to the establishment of immunological tolerance. ..
  68. Qian G, Qin X, Zang Y, Ge B, Guo T, Wan B, et al. High doses of alpha-galactosylceramide potentiate experimental autoimmune encephalomyelitis by directly enhancing Th17 response. Cell Res. 2010;20:480-91 pubmed publisher
    ..Therefore, alpha-GC treatment could improve or worsen EAE by engaging either APCs or Th17/Th1 cells depending on the dose used. ..
  69. Florence W, Xia C, Gordy L, Chen W, Zhang Y, Scott Browne J, et al. Adaptability of the semi-invariant natural killer T-cell receptor towards structurally diverse CD1d-restricted ligands. EMBO J. 2009;28:3579-90 pubmed publisher
    ..Thus, while NKTcrs characteristically use a conserved docking mode, the NKTcr beta-chain allows these cells to recognise unique aspects of structurally diverse CD1d-restricted ligands. ..
  70. Raftery M, Winau F, Giese T, Kaufmann S, Schaible U, Schönrich G. Viral danger signals control CD1d de novo synthesis and NKT cell activation. Eur J Immunol. 2008;38:668-79 pubmed publisher
    ..In conclusion, our data indicate that viral danger signals trigger NKT cell activation by enhancing CD1d de novo synthesis through increasing the abundance of CD1D mRNA in human myeloid DC. ..
  71. Shimizu K, Kurosawa Y, Taniguchi M, Steinman R, Fujii S. Cross-presentation of glycolipid from tumor cells loaded with alpha-galactosylceramide leads to potent and long-lived T cell mediated immunity via dendritic cells. J Exp Med. 2007;204:2641-53 pubmed
    ..Therefore, several immunogenic features of DCs are engaged by the CD1d-mediated cross-presentation of glycolipid-loaded tumor cells, leading to particularly strong and long-lived adaptive immunity. ..
  72. Uemura Y, Liu T, Narita Y, Suzuki M, Nakatsuka R, Araki T, et al. Cytokine-dependent modification of IL-12p70 and IL-23 balance in dendritic cells by ligand activation of Valpha24 invariant NKT cells. J Immunol. 2009;183:201-8 pubmed publisher
    ..These results may account for the long-appreciated contrasting beneficial and adverse consequence of ligand activation of iNKT cells. ..
  73. Tripp C, Sparber F, Hermans I, Romani N, Stoitzner P. Glycolipids injected into the skin are presented to NKT cells in the draining lymph node independently of migratory skin dendritic cells. J Immunol. 2009;182:7644-54 pubmed publisher
    ..In conclusion, migratory skin DC are able to interact with NKT cells; however, intradermally applied glycolipids are presented predominantly by lymph node DC to NKT cells. ..
  74. Kamijuku H, Nagata Y, Jiang X, Ichinohe T, Tashiro T, Mori K, et al. Mechanism of NKT cell activation by intranasal coadministration of alpha-galactosylceramide, which can induce cross-protection against influenza viruses. Mucosal Immunol. 2008;1:208-18 pubmed publisher
    ..These results strengthen the basis of nasal vaccination via NKT cell activation, which can induce immune cross-protection. ..
  75. Stanley A, Zhou Y, Amante F, Randall L, Haque A, Pellicci D, et al. Activation of invariant NKT cells exacerbates experimental visceral leishmaniasis. PLoS Pathog. 2008;4:e1000028 pubmed publisher
    ..Our data clearly illustrate the double-edged sword of NKT cell-based therapy, showing that in some circumstances, such as when sub-clinical or chronic infections exist, iNKT cell activation can have adverse outcomes. ..