Literature DB >> 15722411

Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of alpha-galactosylceramides.

Karl O A Yu1, Jin S Im, Alberto Molano, Yves Dutronc, Petr A Illarionov, Claire Forestier, Nagatoshi Fujiwara, Isa Arias, Sachiko Miyake, Takashi Yamamura, Young-Tae Chang, Gurdyal S Besra, Steven A Porcelli.   

Abstract

A form of alpha-galactosylceramide, KRN7000, activates CD1d-restricted Valpha14-invariant (Valpha14i) natural killer (NK) T cells and initiates multiple downstream immune reactions. We report that substituting the C26:0 N-acyl chain of KRN7000 with shorter, unsaturated fatty acids modifies the outcome of Valpha14i NKT cell activation. One analogue containing a diunsaturated C20 fatty acid (C20:2) potently induced a T helper type 2-biased cytokine response, with diminished IFN-gamma production and reduced Valpha14i NKT cell expansion. C20:2 also exhibited less stringent requirements for loading onto CD1d than KRN7000, suggesting a mechanism for the immunomodulatory properties of this lipid. The differential cellular response elicited by this class of Valpha14i NKT cell agonists may prove to be useful in immunotherapeutic applications.

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Year:  2005        PMID： 15722411      PMCID： PMC552918          DOI： 10.1073/pnas.0407488102

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN： 0027-8424            Impact factor:   11.205


  50 in total

1.  Selective induction of NK cell proliferation and cytotoxicity by activated NKT cells.

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2.  Overexpression of CD1d by keratinocytes in psoriasis and CD1d-dependent IFN-gamma production by NK-T cells.

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3.  Cytometric and functional analyses of NK and NKT cell deficiencies in NOD mice.

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Journal:  Int Immunol       Date:  2001-07       Impact factor: 4.823

4.  The V alpha 14 NKT cell TCR exhibits high-affinity binding to a glycolipid/CD1d complex.

Authors:  Stéphane Sidobre; Olga V Naidenko; Bee-Cheng Sim; Nicholas R J Gascoigne; K Christopher Garcia; Mitchell Kronenberg
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5.  Glycolipid antigen processing for presentation by CD1d molecules.

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Journal:  Science       Date:  2001-01-26       Impact factor: 47.728

6.  alpha-galactosylceramide induces early B-cell activation through IL-4 production by NKT cells.

Authors:  H Kitamura; A Ohta; M Sekimoto; M Sato; K Iwakabe; M Nakui; T Yahata; H Meng; T Koda; S Nishimura; T Kawano; M Taniguchi; T Nishimura
Journal:  Cell Immunol       Date:  2000-01-10       Impact factor: 4.868

7.  Critical contribution of IFN-gamma and NK cells, but not perforin-mediated cytotoxicity, to anti-metastatic effect of alpha-galactosylceramide.

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8.  Costimulation-dependent modulation of experimental autoimmune encephalomyelitis by ligand stimulation of V alpha 14 NK T cells.

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9.  CD1-reactive natural killer T cells are required for development of systemic tolerance through an immune-privileged site.

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  145 in total

1.  Structural basis for the recognition of C20:2-αGalCer by the invariant natural killer T cell receptor-like antibody L363.

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Review 2.  Sphingolipid and glycosphingolipid metabolic pathways in the era of sphingolipidomics.

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Journal:  Chem Rev       Date:  2011-09-26       Impact factor: 60.622

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Journal:  Immunology       Date:  2012-09       Impact factor: 7.397

4.  Expression of CD1c enhances human invariant NKT cell activation by α-GalCer.

Authors:  Lisa M Fox; Jennifer Miksanek; Nathan A May; Louise Scharf; Jennifer L Lockridge; Natacha Veerapen; Gurdyal S Besra; Erin J Adams; Amy W Hudson; Jenny E Gumperz
Journal:  Cancer Immun       Date:  2013-05-10

5.  Engagement of glycosylphosphatidylinositol-anchored proteins results in enhanced mouse and human invariant natural killer T cell responses.

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Journal:  Immunology       Date:  2010-11-11       Impact factor: 7.397

Review 6.  Clinical development of a novel CD1d-binding NKT cell ligand as a vaccine adjuvant.

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Journal:  Clin Immunol       Date:  2010-12-24       Impact factor: 3.969

7.  Structure and function of a potent agonist for the semi-invariant natural killer T cell receptor.

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Review 8.  Potential role of NKT regulatory cell ligands for the treatment of immune mediated colitis.

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9.  Rapid ex vivo expansion of highly enriched human invariant natural killer T cells via single antigenic stimulation for cell therapy to prevent graft-versus-host disease.

Authors:  Abel Trujillo-Ocampo; Hyun-Woo Cho; Amanda C Herrmann; Wilfredo Ruiz-Vazquez; Andrew B Thornton; Hong He; Dan Li; Mariam A Qazilbash; Qing Ma; Steven A Porcelli; Elizabeth J Shpall; Jeffrey Molldrem; Jin S Im
Journal:  Cytotherapy       Date:  2018-07-31       Impact factor: 5.414

10.  An alpha-galactosylceramide C20:2 N-acyl variant enhances anti-inflammatory and regulatory T cell-independent responses that prevent type 1 diabetes.

Authors:  D Ly; R Tohn; B Rubin; H Blumenfeld; G S Besra; N Veerapen; S A Porcelli; T L Delovitch
Journal:  Clin Exp Immunol       Date:  2009-12-15       Impact factor: 4.330
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