Blood:消化道抗原提呈细胞在alloHSCT后GVHD中的重要作用

2019-11-05 QQY MedSci原创

同种异体干细胞移植仍然是治疗高危和/或晚期血液系统恶性肿瘤的基础,但仍受到移植物抗宿主病(GVHD)的限制。GVHD是由受体抗原提呈细胞(APC)与供体T细胞相互作用而引起的,T细胞分化成1型(Th1/Tc1)和17型(Th17/Tc17)致病性T细胞,导致抗原耐受性调节T细胞(Treg/Tr1)模式被破坏。1型和17型T细胞分泌对细胞因子风暴至关重要的细胞因子(如GM-CSF和IFNg),增强供

同种异体干细胞移植仍然是治疗高危和/或晚期血液系统恶性肿瘤的基础,但仍受到移植物抗宿主病(GVHD)的限制。

GVHD是由受体抗原提呈细胞(APC)与供体T细胞相互作用而引起的,T细胞分化成1型(Th1/Tc1)和17型(Th17/Tc17)致病性T细胞,导致抗原耐受性调节T细胞(Treg/Tr1)模式被破坏。1型和17型T细胞分泌对细胞因子风暴至关重要的细胞因子(如GM-CSF和IFNg),增强供体APC扩增极其同种抗原提呈。

目前,越来越明确致病性供体T细胞分化是由专门的受体APC(如树突细胞,DC)和非专门APC(如上皮细胞性和间质细胞性)所启动的,特别是在消化道内。

在移植前后,这些APC会受到来自调节和肠道微生物群的PAMP/DAMP信号的明显影响。随后,消化道的供体DC会被结肠中的DAMP/PAMP信号激活,一旦粘膜屏障被GVHD破坏,这些信号就会到达固有层。从而导致结肠中的供体DC扩增和同种抗原提呈,随后迁移至肠系膜淋巴结。在这里,新的供体T细胞被启动、扩增、分化,并被烙上允许迁移到受损肠道的内脏归巢整合素印迹,最终导致发生致死性的GVHD前馈级联反应。

本文有助于引发我们对启动GVHD的细胞和分子因子的新见解,从而发现许多合理的治疗靶点,此外,本文还强调了抑制消化道APC功能的重要性。

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    2020-08-01 sjq035
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    2019-11-07 膀胱癌
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