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鞘磷脂可调控CD1d限制性抗体呈递
作者:小柯机器人 发布时间:2019/10/22 16:14:05

美国哈佛医学院Richard S. Blumberg和Espen Melum等研究人员合作发现,鞘磷脂参与调控CD1d限制性抗原的呈递与炎症。2019年10月21日,《自然—免疫学》在线发表了这一成果。

研究人员介绍,恒定自然杀伤T(iNKT)细胞识别由CD1d呈现的活化自身和微生物的脂质。CD1d还可以结合非激活脂质,例如鞘磷脂。

研究人员认为它们充当了内源性调节剂,并研究了酸性鞘磷脂酶(ASM)(一种降解鞘磷脂的酶)不足的人和小鼠。研究人员发现,小鼠中ASM缺失会导致胸腺中CD1d限制性抗原呈递和iNKT细胞选择的减少,从而导致iNKT细胞水平降低和对iNKT细胞介导的炎症条件的抵抗。在患有Niemann–Pick病的ASM缺乏者中也观察到抗原呈递缺陷和iNKT细胞减少,而健康人的ASM活性与iNKT细胞表型相关。ASM药理调控可促进抗原呈递并恢复ASM缺陷小鼠的iNKT细胞水平。

总之,这些结果表明,非激动性CD1d相关脂质的控制对于iNKT细胞的发育和体内功能至关重要,并且体现了细胞鞘脂代谢与免疫力之间的紧密联系。

附:英文原文
 
Title:Control of CD1d-restricted antigen presentation and inflammation by sphingomyelin
 
Author:Espen Melum, Xiaojun Jiang, Kristi D. Baker, M. Fatima Macedo, Jürgen Fritsch, C. Marie Dowds, Jing Wang, Anne Pharo, Arthur Kaser, Corey Tan, Catia S. Pereira, Samuel L. Kelly, Jingjing Duan, Tom H. Karlsen, Mark A. Exley, Stefan Schütze, Dirk M. Zajonc, Alfred H. Merrill, Edward H. Schuchman, Sebastian Zeissig & Richard S. Blumberg
 
Issue&Volume:21 October 2019
 
Abstract: 
 
Invariant natural killer T (iNKT) cells recognize activating self and microbial lipids presented by CD1d. CD1d can also bind non-activating lipids, such as sphingomyelin. We hypothesized that these serve as endogenous regulators and investigated humans and mice deficient in acid sphingomyelinase (ASM), an enzyme that degrades sphingomyelin. We show that ASM absence in mice leads to diminished CD1d-restricted antigen presentation and iNKT cell selection in the thymus, resulting in decreased iNKT cell levels and resistance to iNKT cell-mediated inflammatory conditions. Defective antigen presentation and decreased iNKT cells are also observed in ASM-deficient humans with Niemann–Pick disease, and ASM activity in healthy humans correlates with iNKT cell phenotype. Pharmacological ASM administration facilitates antigen presentation and restores the levels of iNKT cells in ASM-deficient mice. Together, these results demonstrate that control of non-agonistic CD1d-associated lipids is critical for iNKT cell development and function in vivo and represents a tight link between cellular sphingolipid metabolism and immunity.
 
DOI:10.1038/s41590-019-0504-0
 
Source: https://www.nature.com/articles/s41590-019-0504-0

期刊信息

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex