title: Plasma phospholipid transfer protein (PLTP) modulates adaptive immune functions through alternation of T helper cell polarization.
abstract: Plasma phospholipid transfer protein (PLTP) is a key determinant of lipoprotein metabolism, and both animal and human studies converge to indicate that PLTP promotes atherogenesis and its thromboembolic complications. Moreover, it has recently been reported that PLTP modulates inflammation and immune responses. Although earlier studies from our group demonstrated that PLTP can modify macrophage activation, the implication of PLTP in the modulation of T-cell-mediated immune responses has never been investigated and was therefore addressed in the present study. Approach and results: In the present study, we demonstrated that PLTP deficiency in mice has a profound effect on CD4+Th0 cell polarization, with a shift towards the anti-inflammatory Th2 phenotype under both normal and pathological conditions. In a model of contact hypersensitivity, a significantly impaired response to skin sensitization with the hapten-2,4-dinitrofluorobenzene (DNFB) was observed in PLTP-deficient mice compared to wild-type (WT) mice. Interestingly, PLTP deficiency in mice exerted no effect on the counts of total white blood cells, lymphocytes, granulocytes, or monocytes in the peripheral blood. Moreover, PLTP deficiency did not modify the amounts of CD4+and CD8+T lymphocyte subsets. However, PLTP-deficiency, associated with upregulation of the Th2 phenotype, was accompanied by a significant decrease in the production of the pro-Th1 cytokine interleukin 18 by accessory cells.
  
  
  
  For the first time, this work reports a physiological role for PLTP in the polarization of CD4+T cells toward the pro-inflammatory Th1 phenotype.
authors: INSERM UMR866 - F21079 Dijon, France.|Univ. Bourgogne Franche-Comté, F-21000 Dijon, France.|LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne-Franche Comté, F-21000 Dijon, France.
authors: Catherine
authors: C
authors: Desrumaux
authors: INSERM UMR866 - F21079 Dijon, France.|Univ. Bourgogne Franche-Comté, F-21000 Dijon, France.|LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne-Franche Comté, F-21000 Dijon, France.|CHU, Hôpital du Bocage, Dijon, France.
authors: Stéphanie
authors: S
authors: Lemaire-Ewing
authors: INSERM UMR866 - F21079 Dijon, France.|Univ. Bourgogne Franche-Comté, F-21000 Dijon, France.|LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne-Franche Comté, F-21000 Dijon, France.
authors: Nicolas
authors: N
authors: Ogier
authors: INSERM UMR866 - F21079 Dijon, France.|Univ. Bourgogne Franche-Comté, F-21000 Dijon, France.|LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne-Franche Comté, F-21000 Dijon, France.
authors: Akadiri
authors: A
authors: Yessoufou
authors: INSERM UMR866 - F21079 Dijon, France.|LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne-Franche Comté, F-21000 Dijon, France.|CHU, Hôpital du Bocage, Dijon, France.
authors: Arlette
authors: A
authors: Hammann
authors: Univ. Bourgogne Franche-Comté, F-21000 Dijon, France.|Plateforme de Cytométrie en Flux, Université de Bourgogne, Dijon, France.
authors: Anabelle
authors: A
authors: Sequeira-Le Grand
authors: INSERM UMR866 - F21079 Dijon, France.|Univ. Bourgogne Franche-Comté, F-21000 Dijon, France.|LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne-Franche Comté, F-21000 Dijon, France.
authors: Valérie
authors: V
authors: Deckert
authors: INSERM UMR866 - F21079 Dijon, France.|Univ. Bourgogne Franche-Comté, F-21000 Dijon, France.|LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne-Franche Comté, F-21000 Dijon, France.
authors: Jean-Paul
authors: JP
authors: Pais de Barros
authors: INSERM UMR866 - F21079 Dijon, France.|Univ. Bourgogne Franche-Comté, F-21000 Dijon, France.|LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne-Franche Comté, F-21000 Dijon, France.
authors: Naïg
authors: N
authors: Le Guern
authors: CHU, Hôpital du Bocage, Dijon, France.
authors: Julien
authors: J
authors: Guy
authors: INSERM UMR866 - F21079 Dijon, France.|Univ. Bourgogne Franche-Comté, F-21000 Dijon, France.|LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne-Franche Comté, F-21000 Dijon, France.
authors: Naim A
authors: NA
authors: Khan
authors: INSERM UMR866 - F21079 Dijon, France.|Univ. Bourgogne Franche-Comté, F-21000 Dijon, France.|LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne-Franche Comté, F-21000 Dijon, France.|CHU, Hôpital du Bocage, Dijon, France.
authors: Laurent
authors: L
authors: Lagrost
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D016764:Cell Polarity / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000378:metabolism; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000473:pathology; D007958:Leukocyte Count; D008810:Mice, Inbred C57BL; D049294:Phospholipid Transfer Proteins / Q000172:deficiency / Q000378:metabolism*; D013154:Spleen / Q000166:cytology; D020825:T-Box Domain Proteins / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: D015415:Biomarkers; D016207:Cytokines; D050990:GATA3 Transcription Factor; D049294:Phospholipid Transfer Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C510091:phospholipid transfer protein, mouse