Objective： 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 ...Objective： 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＋ ThO 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-Thl cytokine interleukin 18 by accessory cells. Conclusions： For the first time, this work reports a physiological role for PLTP in the polarization of CD4＋ T cells toward the pro-inflammatory Th I phenotype.展开更多
Plasma phospholipid transfer protein(PLTP)is a multifunctional lipid transporter.In addition to phospholipids,PLTP transports various amphipathic compounds,such as cholesterol,alphatocopherol,diacylglycerides,and lipo...Plasma phospholipid transfer protein(PLTP)is a multifunctional lipid transporter.In addition to phospholipids,PLTP transports various amphipathic compounds,such as cholesterol,alphatocopherol,diacylglycerides,and lipopolysaccharides.In addition to its impact on lipid metabolism and atherosclerosis development,PLTP has recently been reported to modulate inflammation and immune responses.It modulates the phagocytic activity of macrophages and microglial cells1,2 and increases the production of the pro-inflammatory cytokine interleukin 6(IL-6).3–5 In further support of the pro-inflammatory effect of PLTP,the expression level of IL-6 and the number of infiltrating macrophages in aortic tissue after experimental aneurysm induction were shown to be lower in PLTP-deficient mice than in wild-type mice;6 additionally,recombinant PLTP was shown to exert a direct pro-inflammatory effect on rheumatoid arthritis fibroblast-like synoviocytes,independent of its lipid transfer activity.7 Notably,despite its direct pro-inflammatory actions,PLTP can exert indirect antiinflammatory actions through its ability to transport and detoxify lipopolysaccharides in gram-negative bacteria.8,9 In humans,the majority of PLTP-associated proteins are involved in innate immunity and/or the inflammatory response in plasma,and PLTP activity is significantly increased in patients with bacterial infections and systemic inflammation.In addition to the key roles of PLTP in innate immunity,a recent publication from our group entitled“Plasma phospholipid transfer protein(PLTP)modulates adaptive immune functions through alternation of T-helper-cell polarization”10 demonstrated for the first time that PLTP can also modulate adaptive immune responses.This modulation occurred through a profound effect on CD4+T-cell polarization toward the pro-inflammatory Th1 subtype.This novel property also supports the pro-inflammatory and pro-atherogenic effects of PLTP(Fig.1).展开更多
文摘Objective： 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＋ ThO 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-Thl cytokine interleukin 18 by accessory cells. Conclusions： For the first time, this work reports a physiological role for PLTP in the polarization of CD4＋ T cells toward the pro-inflammatory Th I phenotype.
文摘Plasma phospholipid transfer protein(PLTP)is a multifunctional lipid transporter.In addition to phospholipids,PLTP transports various amphipathic compounds,such as cholesterol,alphatocopherol,diacylglycerides,and lipopolysaccharides.In addition to its impact on lipid metabolism and atherosclerosis development,PLTP has recently been reported to modulate inflammation and immune responses.It modulates the phagocytic activity of macrophages and microglial cells1,2 and increases the production of the pro-inflammatory cytokine interleukin 6(IL-6).3–5 In further support of the pro-inflammatory effect of PLTP,the expression level of IL-6 and the number of infiltrating macrophages in aortic tissue after experimental aneurysm induction were shown to be lower in PLTP-deficient mice than in wild-type mice;6 additionally,recombinant PLTP was shown to exert a direct pro-inflammatory effect on rheumatoid arthritis fibroblast-like synoviocytes,independent of its lipid transfer activity.7 Notably,despite its direct pro-inflammatory actions,PLTP can exert indirect antiinflammatory actions through its ability to transport and detoxify lipopolysaccharides in gram-negative bacteria.8,9 In humans,the majority of PLTP-associated proteins are involved in innate immunity and/or the inflammatory response in plasma,and PLTP activity is significantly increased in patients with bacterial infections and systemic inflammation.In addition to the key roles of PLTP in innate immunity,a recent publication from our group entitled“Plasma phospholipid transfer protein(PLTP)modulates adaptive immune functions through alternation of T-helper-cell polarization”10 demonstrated for the first time that PLTP can also modulate adaptive immune responses.This modulation occurred through a profound effect on CD4+T-cell polarization toward the pro-inflammatory Th1 subtype.This novel property also supports the pro-inflammatory and pro-atherogenic effects of PLTP(Fig.1).
