替代拼接将人类的CD137从辅助刺激功能转化为免疫抑制功能.
Manuel Rojas1, Luke S Heuer2, Weici Zhang2
1Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, Davis, CA, United States; Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia.
Journal of autoimmunity
|November 8, 2025
概括
可溶性CD137 (sCD137) 拼接变体,与它们的膜结合对应物不同,表现出免疫抑制性质. 这些新型的sCD137变种显示出作为治疗炎症和自身免疫性疾病的新治疗策略的潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 膜结合的CD137 (mCD137) 是一种已知的辅助刺激分子.
- 替代拼接生成具有未知的功能的可溶性CD137 (sCD137) 转录.
研究的目的:
- 研究人类sCD137拼接变体的结构,功能和治疗潜力.
- 为了比较sCD137与mCD137.7的特性.
主要方法:
- sCD137异形结构的表征.
- 在激活的人类调节性T细胞 (Tregs) 中分析sCD137表达.
- 重组Fc-Hu-sCD137变异的工程和对它们对T细胞功能的影响的评估.
- 对mTOR路径参与的评估.
主要成果:
- sCD137异型缺乏CRD4区域,并且具有独特的结构.
- 活化的人类Tregs表达sCD137的两种异型,识别特定的Treg表型.
- 工程设计的sCD137变体表现出免疫抑制活性,抑制T细胞增殖和IFN-γ分泌.
- sCD137介导的免疫抑制包括对mTORC1通路 (S6和4EBP1) 的下调.
结论:
- 人类sCD137变种具有免疫抑制作用,与辅助刺激的mCD137.7形成鲜明对比.
- sCD137变种代表了潜在的新型治疗点,用于炎症和自身免疫性疾病.
相关概念视频
Alternative RNA Splicing
24.6K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
24.6K
RNA Splicing
60.3K
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
60.3K
T Cell Activation and Clonal Selection
14.6K
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
14.6K
Regulation of Hematopoietic Stem Cells
3.9K
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.9K
B Cell Activation and Differentiation
15.9K
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
15.9K
Exon Recombination
4.1K
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...
Exon shuffling follows “splice frame rules.” Each exon...
4.1K


