纳塔利祖马布治疗诱导益炎性CD4T细胞,首选在集成蛋白β7+区间
Mélanie Nguyen Ky1, Adrien Duran1, Iris Hasantari1
1From the Immunoconcept (M.N.K., A.D., I.H., A.B., N.S.), CNRS UMR 5164, University of Bordeaux; Service de Neurologie (M.D., A.R.), CRC SEP, Centre Hospitalier Universitaire (CHU) de Bordeaux; and INSERM U 1215 (B.B., A.R.), Neurocentre Magendie, University of Bordeaux, France.
Neurology(R) neuroimmunology & neuroinflammation
|September 22, 2023
概括
对MS的纳塔利祖马布治疗增加了表达整合素β7的益炎性肠导记忆CD4 T细胞. 这些细胞可能在停止纳塔利祖马布后驱动疾病复发,突出显示MS复发的潜在机制.
科学领域:
- 免疫学 免疫学 免疫学
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
背景情况:
- 纳塔利祖马布是一种单克隆抗体,通过阻断淋巴细胞进入中枢神经系统来治疗复发性缓解性多发性硬化.
- 停止纳塔利祖马布治疗,特别是JC病毒重新激活时,可能导致20%的患者出现疾病复发.
- 纳塔利祖马布诱导疾病反弹的机制尚不清楚,但它与增加的炎症性CD4T细胞有关.
研究的目的:
- 在接受纳塔利祖马布治疗的多发性硬化症患者中研究肠道衍生的CD4 T细胞的表型和细胞因子概况.
- 为了确定纳塔利祖马布是否会影响来自肠道的记忆CD4T细胞的特性.
- 探索这些细胞在多发性硬化病原和反弹现象中的潜在作用.
主要方法:
- 通过整体蛋白β7表达来识别肠道衍生的记忆CD4 T细胞.
- 整合素β7+和整合素β7- CD4 T 细胞在健康捐赠者和多发性硬化症患者 (有/没有纳塔利祖马布) 的比较.
- 在体外评估CD4 T细胞子集穿越血脑屏障模型的转移.
主要成果:
- 纳塔利祖马布治疗的患者在他们的整体蛋白β7+记忆CD4T细胞中显示出更高比例的促炎Th17/Th1细胞,包括IL-17A+IFNγ+和IL-17A+GM-CSF+细胞.
- 在纳塔利祖马布治疗下,整体β7记忆CD4T细胞仅在Th17/Th1细胞中略有增加.
- 整合素β7+和整合素β7-Th17/Th1细胞在大脑微血管内皮细胞模型中表现出类似的迁移效率.
结论:
- 在纳塔利祖马布治疗的多发性硬化症患者中,循环整合素β7+记忆 CD4 T 细胞被增添了亲炎细胞.
- 这些发现支持了一个假设,即整合素β7+记忆CD4T细胞有助于在停止纳塔利祖马布治疗后,MS疾病反弹的潜在病原机制.
- 对整合素β7+记忆CD4T细胞的进一步研究可以阐明MS的发病过程,并为治疗策略提供信息.
相关概念视频
01:24Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
164
Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
164
01:24T Cell Types and Functions
1.1K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.1K
01:22T Cell Activation and Clonal Selection
787
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...
787
01:15Activation of Integrins
3.5K
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
3.5K
01:17Intracellular Signaling Affects Focal Adhesions
2.7K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.7K