title: Genome-wide immunity studies in the rabbit: transcriptome variations in peripheral blood mononuclear cells after in vitro stimulation by LPS or PMA-Ionomycin.
abstract: BACKGROUND
  Our purpose was to obtain genome-wide expression data for the rabbit species on the responses of peripheral blood mononuclear cells (PBMCs) after in vitro stimulation by lipopolysaccharide (LPS) or phorbol myristate acetate (PMA) and ionomycin. This transcriptome profiling was carried out using microarrays enriched with immunity-related genes, and annotated with the most recent data available for the rabbit genome.
  
  
  RESULTS
  The LPS affected 15 to 20 times fewer genes than PMA-Ionomycin after both 4 hours (T4) and 24 hours (T24), of in vitro stimulation, in comparison with mock-stimulated PBMCs. LPS induced an inflammatory response as shown by a significant up-regulation of IL12A and CXCL11 at T4, followed by an increased transcription of IL6, IL1B, IL1A, IL36, IL37, TNF, and CCL4 at T24. Surprisingly, we could not find an up-regulation of IL8 either at T4 or at T24, and detected a down-regulation of DEFB1 and BPI at T24. A concerted up-regulation of SAA1, S100A12 and F3 was found upon stimulation by LPS. PMA-Ionomycin induced a very early expression of Th1, Th2, Treg, and Th17 responses by PBMCs at T4. The Th1 response increased at T24 as shown by the increase of the transcription of IFNG and by contrast to other cytokines which significantly decreased from T4 to T24 (IL2, IL4, IL10, IL13, IL17A, CD69) by comparison to mock-stimulation. The granulocyte-macrophage colony-stimulating factor (CSF2) was by far the most over-expressed gene at both T4 and T24 by comparison to mock-stimulated cells, confirming a major impact of PMA-Ionomycin on cell growth and proliferation. A significant down-regulation of IL16 was observed at T4 and T24, in agreement with a role of IL16 in PBMC apoptosis.
  
  
  CONCLUSIONS
  We report new data on the responses of PBMCs to LPS and PMA-Ionomycin in the rabbit species, thus enlarging the set of mammalian species for which such reports exist. The availability of the rabbit genome assembly together with high throughput genomic tools should pave the way for more intense genomic studies for this species, which is known to be a very relevant biomedical model in immunology and physiology.
authors.affiliation: INRA, UMR 1313 Génétique Animale et Biologie Intégrative, Domaine de Vilvert, F-78350, Jouy-en-Josas, France. vincent.jacquier@toulouse.inra.fr.|AgroParisTech, UMR 1313 Génétique Animale et Biologie Intégrative, Domaine de Vilvert, F-78350, Jouy-en-Josas, France. vincent.jacquier@toulouse.inra.fr.|INRA, GenPhySE (Génétique, Physiologie et Systèmes d'Elevage), F-31326, Castanet-Tolosan, France. vincent.jacquier@toulouse.inra.fr.|Université de Toulouse, INP, ENSAT, GenPhySE (Génétique, Physiologie et Systèmes d'Elevage), F-31326, Castanet-Tolosan, France. vincent.jacquier@toulouse.inra.fr.|Université de Toulouse, INP, ENVT, GenPhySE (Génétique, Physiologie et Systèmes d'Elevage), F-31076, Toulouse, France. vincent.jacquier@toulouse.inra.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Jacquier
authors.affiliation: INRA, UMR 1313 Génétique Animale et Biologie Intégrative, Domaine de Vilvert, F-78350, Jouy-en-Josas, France. Jordi.Estelle@jouy.inra.fr.|AgroParisTech, UMR 1313 Génétique Animale et Biologie Intégrative, Domaine de Vilvert, F-78350, Jouy-en-Josas, France. Jordi.Estelle@jouy.inra.fr.
authors.forename: Jordi
authors.initials: J
authors.lastname: Estellé
authors.affiliation: INRA, UMR1198 Biologie du Développement et Reproduction, Domaine de Vilvert, F-78350, Jouy-en-Josas, France. barbara.panneau@jouy.inra.fr.
authors.forename: Barbara
authors.initials: B
authors.lastname: Schmaltz-Panneau
authors.affiliation: INRA, UMR 1313 Génétique Animale et Biologie Intégrative, Domaine de Vilvert, F-78350, Jouy-en-Josas, France. jerome.lecardonnel@jouy.inra.fr.|AgroParisTech, UMR 1313 Génétique Animale et Biologie Intégrative, Domaine de Vilvert, F-78350, Jouy-en-Josas, France. jerome.lecardonnel@jouy.inra.fr.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Lecardonnel
authors.affiliation: INRA, UMR 1313 Génétique Animale et Biologie Intégrative, Domaine de Vilvert, F-78350, Jouy-en-Josas, France. marco.moroldo@jouy.inra.fr.|AgroParisTech, UMR 1313 Génétique Animale et Biologie Intégrative, Domaine de Vilvert, F-78350, Jouy-en-Josas, France. marco.moroldo@jouy.inra.fr.
authors.forename: Marco
authors.initials: M
authors.lastname: Moroldo
authors.affiliation: INRA, UMR 1313 Génétique Animale et Biologie Intégrative, Domaine de Vilvert, F-78350, Jouy-en-Josas, France. gaetan.lemonnier@jouy.inra.fr.|AgroParisTech, UMR 1313 Génétique Animale et Biologie Intégrative, Domaine de Vilvert, F-78350, Jouy-en-Josas, France. gaetan.lemonnier@jouy.inra.fr.
authors.forename: Gaëtan
authors.initials: G
authors.lastname: Lemonnier
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. jturner@broadinstitute.org.
authors.forename: Jason
authors.initials: J
authors.lastname: Turner-Maier
authors.affiliation: INRA, UMR1198 Biologie du Développement et Reproduction, Domaine de Vilvert, F-78350, Jouy-en-Josas, France. veronique.duranthon@jouy.inra.fr.
authors.forename: Véronique
authors.initials: V
authors.lastname: Duranthon
authors.affiliation: INRA, UMR1331, Toxalim, Research Center in Food Toxicology, 180 chemin de Tournefeuille, BP 93173, F-31027, Toulouse, France. ioswald@toulouse.inra.fr.|Université de Toulouse, INP, UMR1331, Toxalim, Research Center in Food Toxicology, F-31000, Toulouse, France. ioswald@toulouse.inra.fr.
authors.forename: Isabelle P
authors.initials: IP
authors.lastname: Oswald
authors.affiliation: INRA, GenPhySE (Génétique, Physiologie et Systèmes d'Elevage), F-31326, Castanet-Tolosan, France. thierry.gidenne@toulouse.inra.fr.|Université de Toulouse, INP, ENSAT, GenPhySE (Génétique, Physiologie et Systèmes d'Elevage), F-31326, Castanet-Tolosan, France. thierry.gidenne@toulouse.inra.fr.|Université de Toulouse, INP, ENVT, GenPhySE (Génétique, Physiologie et Systèmes d'Elevage), F-31076, Toulouse, France. thierry.gidenne@toulouse.inra.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Gidenne
authors.affiliation: INRA, UMR 1313 Génétique Animale et Biologie Intégrative, Domaine de Vilvert, F-78350, Jouy-en-Josas, France. claire.rogel-gaillard@jouy.inra.fr.|AgroParisTech, UMR 1313 Génétique Animale et Biologie Intégrative, Domaine de Vilvert, F-78350, Jouy-en-Josas, France. claire.rogel-gaillard@jouy.inra.fr.
authors.forename: Claire
authors.initials: C
authors.lastname: Rogel-Gaillard
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D016678:Genome; D007109:Immunity / Q000235:genetics*; D015759:Ionomycin / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D059467:Transcriptome / Q000187:drug effects
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate