Focus on the controversial activation of human iNKT cells by 4-deoxy analogue of KRN7000.
4-Deoxy-alpha-GalCer analogues are considered weaker agonists than KRN7000 for the stimulation of human iNKT cells, but this remains strongly debated. In this work, we described a strategy toward 4-deoxy-alpha-GalCers with, as a key step, a metathesis reaction allowing sphingosine modifications from a single ethylenic alpha-galactoside precursor. The 4-deoxy-KRN7000 derivative 2, described here, induced potent cytokinic responses, comparable to those of KRN7000, both from human iNKT cells in vitro and from their murine counterpart in vivo.
Lacône
Vivien
V
Université de Nantes, CNRS, Chimie et Interdisciplinarité: Synthèse, Analyse, Modélisation (CEISAM), UMR CNRS 6230, Faculté des Sciences et des Techniques, 2 Rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France.
Hunault
Julie
J
Pipelier
Muriel
M
Blot
Virginie
V
Lecourt
Thomas
T
Rocher
Jézabelle
J
Turcot-Dubois
Anne-Laure
AL
Marionneau
Séverine
S
Douillard
Jean-Yves
JY
Clément
Monique
M
Le Pendu
Jacques
J
Bonneville
Marc
M
Micouin
Laurent
L
Dubreuil
Didier
D
D000276:Adjuvants, Immunologic / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D005699:Galactosylceramides / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D055611:Natural Killer T-Cells / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D005699:Galactosylceramides; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; C103873:KRN 7000