Modulation of CD1d-restricted NKT cell responses by usingN-acyl variants of α-galactosylceramides
| Autor: | Karl O.A. Yu, Claire Forestier, Alberto Molano, Petr A. Illarionov, Jin S. Im, Isa Arias, Sachiko Miyake, Takashi Yamamura, Yves Dutronc, Nagatoshi Fujiwara, Gurdyal S. Besra, Steven A. Porcelli, Young-Tae Chang |
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| Rok vydání: | 2005 |
| Předmět: |
Galactosylceramides
Cell chemical and pharmacologic phenomena Inflammation medicine.disease_cause Flow cytometry Autoimmunity Mice medicine Animals Mice Knockout chemistry.chemical_classification Multidisciplinary biology medicine.diagnostic_test Fatty acid Biological Sciences Flow Cytometry Cytokine response Cell biology Killer Cells Natural Mice Inbred C57BL medicine.anatomical_structure Biochemistry chemistry CD1D biology.protein lipids (amino acids peptides and proteins) medicine.symptom |
| Zdroj: | Proceedings of the National Academy of Sciences. 102:3383-3388 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0407488102 |
| Popis: | A form of α-galactosylceramide, KRN7000, activates CD1d-restricted Vα14-invariant (Vα14i) natural killer (NK) T cells and initiates multiple downstream immune reactions. We report that substituting the C26:0N-acyl chain of KRN7000 with shorter, unsaturated fatty acids modifies the outcome of Vα14i 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-γ production and reduced Vα14i 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 Vα14i NKT cell agonists may prove to be useful in immunotherapeutic applications. |
| Databáze: | OpenAIRE |
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