title: Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of alpha-galactosylceramides.
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.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Karl O A
authors.initials: KO
authors.lastname: Yu
authors.forename: Jin S
authors.initials: JS
authors.lastname: Im
authors.forename: Alberto
authors.initials: A
authors.lastname: Molano
authors.forename: Yves
authors.initials: Y
authors.lastname: Dutronc
authors.forename: Petr A
authors.initials: PA
authors.lastname: Illarionov
authors.forename: Claire
authors.initials: C
authors.lastname: Forestier
authors.forename: Nagatoshi
authors.initials: N
authors.lastname: Fujiwara
authors.forename: Isa
authors.initials: I
authors.lastname: Arias
authors.forename: Sachiko
authors.initials: S
authors.lastname: Miyake
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamura
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Chang
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
mesh_terms: D000818:Animals; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D005699:Galactosylceramides; C103873:KRN 7000
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