Bagley Jessamyn, Williams Linus, Hyde Michael, Birriel Christian Rosa, Iacomini John
Tufts University School of Medicine, Department of Immunology, Sackler School of Biomedical Sciences Programs in Immunology and Genetics, Boston, MA 02111 USA.
Curr Transplant Rep. 2019 Mar;6(1):90-98. doi: 10.1007/s40472-019-0232-2. Epub 2019 Feb 26.
Advances in the development of immunosuppressive drug regimens have led to impressive survival rates in the year following organ transplantation. However rates of long-term graft dysfunction remain undesirably high. Recently it has been shown that co-morbidities in the patient population may affect graft survival. In mouse models, hyperlipidemia, a co-morbidity present in the majority of cardiac transplant patients, can significantly alter T cell responses to cardiac and skin allografts, and accelerate graft rejection. Here we review recent advances in our understanding of how alterations in lipids affect immune function and graft survival.
Recent work in humans has highlighted the importance of controlling low density lipoprotein (LDL) levels in transplant recipients to reduce the development of chronic allograft vasculopathy (CAV). High serum levels of cholesterol containing particles leads to extensive immune system changes to T cell proliferation, differentiation and suppression. Changes in B cell subsets, and the ability of antigen presenting cells to stimulate T cells in hyperlipidemic animals may also contribute to increased organ allograft rejection.
Cholesterol metabolism is a critical cellular pathway for proper control of immune cell homeostasis and activation. Increasing evidence in both human, and in mouse models shows that elevated levels of serum cholesterol can have profound impact on the immune system. Hyperlipidemia has been shown to increase T cell activation, alter the development of T helper subsets, increase the inflammatory capacity of antigen presenting cells (APC) and significantly accelerate graft rejection in several models.
免疫抑制药物治疗方案的进展使器官移植后第一年的生存率令人瞩目。然而，长期移植物功能障碍的发生率仍然高得不理想。最近有研究表明，患者群体中的合并症可能会影响移植物存活。在小鼠模型中，高脂血症是大多数心脏移植患者存在的一种合并症，可显著改变T细胞对心脏和皮肤同种异体移植物的反应，并加速移植物排斥反应。在此，我们综述了在理解脂质改变如何影响免疫功能和移植物存活方面的最新进展。
最近在人类中的研究强调了控制移植受者低密度脂蛋白（LDL）水平以减少慢性同种异体移植物血管病变（CAV）发生的重要性。高血清水平的含胆固醇颗粒会导致免疫系统对T细胞增殖、分化和抑制产生广泛变化。高脂血症动物中B细胞亚群的变化以及抗原呈递细胞刺激T细胞的能力也可能导致器官同种异体移植物排斥反应增加。
胆固醇代谢是正确控制免疫细胞稳态和激活的关键细胞途径。越来越多的人类和小鼠模型证据表明，血清胆固醇水平升高可对免疫系统产生深远影响。高脂血症已被证明会增加T细胞活化，改变辅助性T细胞亚群的发育，增加抗原呈递细胞（APC）的炎症能力，并在多个模型中显著加速移植物排斥反应。
