人类的XIAP缺乏会导致X链接的淋巴增殖综合征
Stéphanie Rigaud1, Marie-Claude Fondanèche, Nathalie Lambert
1Inserm 768, Laboratoire du Développement Normal et Pathologique du Système Immunitaire, Univ. René Descartes, Paris, F-75015, France.
Nature
|November 3, 2006
概括
在X结合抑制细胞灭亡 (XIAP) 基因的突变导致X结合淋巴增殖综合征 (XLP),导致淋巴细胞灭亡增加和减少自然杀手T淋巴细胞 (NKT细胞). 这一发现突出了XIAP的发现.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 免疫平衡依赖于受控的淋巴细胞增殖和亡.
- 免疫恒常的缺陷可以导致淋巴增殖障碍,如X链接淋巴增殖综合征 (XLP).
- 信号淋巴细胞激活分子 (SLAM) 相关蛋白 (SAP) 的突变导致60%的家族XLP病例.
研究的目的:
- 在缺乏SAP突变的患者中确定XLP的遗传原因.
- 调查X链接的亡抑制剂 (XIAP) 在淋巴细胞稳态和XLP中的作用.
主要方法:
- 基因测序以确定XIAP基因中的突变.
- 评估淋巴细胞对各种刺激的反应中的亡 (TCR-CD3,CD95,TRAIL-R).
- 在XIAP缺乏患者中量化自然杀手T淋巴细胞 (NKT细胞) 数量.
主要成果:
- 在没有SAP突变的XLP患者中发现了XIAP基因的突变,导致XIAP表达有缺陷.
- 缺乏XIAP的淋巴细胞在刺激时表现出增强的亡.
- 缺乏XIAP的患者显示NKT细胞数量减少,类似于缺乏SAP的患者.
结论:
- XIAP突变导致XLP,表明XIAP在调节淋巴细胞平衡中的关键作用.
- XIAP对于NKT细胞的存活和/或分化至关重要.
- 在XIAP和SAP缺陷患者之间NKT细胞的共享缺陷支持NKT细胞在EBV免疫力中的作用.
更多相关视频
08:17A Human Peripheral Blood Mononuclear Cell (PBMC) Engrafted Humanized Xenograft Model for Translational Immuno-oncology (I-O) Research
Published on: August 15, 2019
07:45Draining Lymph Node Metastasis Model for Assessing the Dynamics of Antigen-Specific CD8+ T Cells During Tumorigenesis
Published on: January 26, 2024
相关概念视频
Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
X-Inactivation
The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.
Inheritance of Chromatin Structures
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...
X-inactivation
The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.
Exon Recombination
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Immunodeficiency Diseases
Immunodeficiency disorders are conditions in which the immune system's ability to fight infectious disease and cancer is compromised or entirely absent. The immune system comprises a complex network of cells, tissues, and organs that work together to protect the body from potentially harmful invaders. When this system is deficient or not functioning properly, it leaves the body susceptible to infections, diseases, or other complications.
There are three main causes of immunodeficiency disorders...
There are three main causes of immunodeficiency disorders...
