Expression of functional GPR35 in human iNKT cells.
The aim of this study was to examine the expression of G protein-coupled receptor (GPR)35 in human invariant natural killer T (iNKT) cells and to determine the functional effects induced by selective activation of this receptor. RT-PCR analysis showed that both human iNKT cells and resting PBMC expressed GPR35; GPR35 protein resulted mostly localized in the plasma membrane, while it internalized in punctate intracellular structures following specific receptor activation (Western blot and immunofluorescence/confocal microscopy analysis). The specific activation of GPR35 by selective receptor agonists [l-kynurenic acid (KYNA)] or 1,4-dihydro-5-(2-propoxyphenyl)-7H-1,2,3-triazolo [4,5-d]pyrimidine-7-one (zaprinast)] functionally correlated with a significant reduction in IL-4 release from alpha-galactosylceramide (alpha-GalCer)-activated human iNKT cells, and this effect resulted mediated by pertussis toxin (PTX)-sensitive Gi/o proteins. In conclusion, our results demonstrate that human iNKT cells express GPR35 functionally active in reducing IL-4 release.
Fallarini
Silvia
S
Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche (DISCAFF), University of Piemonte Orientale Amedeo Avogadro, Via Giovanni Bovio, 6, 28100 Novara, Italy.
Magliulo
Laura
L
Paoletti
Tiziana
T
de Lalla
Claudia
C
Lombardi
Grazia
G
D002462:Cell Membrane / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D007736:Kynurenic Acid / Q000494:pharmacology; D055611:Natural Killer T-Cells / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
C111379:GPR35 protein, human; D011688:Purinones; D043562:Receptors, G-Protein-Coupled; D015847:Interleukin-4; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C011145:zaprinast; D007736:Kynurenic Acid