Danger Signals and Graft-versus-host Disease: Current Understanding and Future Perspectives.

Danger Signals and Graft-versus-host Disease: Current Understanding and Future Perspectives.
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DOI:
10.3389/fimmu.2016.00539
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发表时间:
2016
影响因子:
7.3
通讯作者:
Reddy P
Reddy P
中科院分区:
医学2区
文献类型:
--
作者:
Toubai T;Mathewson ND;Magenau J;Reddy P

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异基因造血干细胞移植(allo-HCT)后的移植物抗宿主反应是人类中观察到的最强烈的炎症反应之一。宿主调节促进了供体细胞的植入,但由此引起的组织损伤引发了急性移植物抗宿主病(GVHD)发展的关键第一步。组织损伤通过释放危险刺激物(如损伤相关分子模式(DAMP)和病原体相关分子模式(PAMP))广泛刺激模式识别受体(PRR)释放促炎细胞因子(如TNF-α、IL-1β和IL-6)。DAMP和PAMP作为宿主和供体来源的抗原呈递细胞(APC)的有效刺激物起作用,所述抗原呈递细胞继而激活和放大同种异体反应性供体T细胞的应答。新出现的数据还指出了APC和供体T细胞抑制DAMP诱导的炎症在减轻GVHD严重程度中的作用。本文就危险刺激物如DAMPs和PAMPs在GVHD中的作用作一综述。
Graft-versus-host response after allogeneic hematopoietic stem cell transplantation (allo-HCT) represents one of the most intense inflammatory responses observed in humans. Host conditioning facilitates engraftment of donor cells, but the tissue injury caused from it primes the critical first steps in the development of acute graft-versus-host disease (GVHD). Tissue injuries release pro-inflammatory cytokines (such as TNF-α, IL-1β, and IL-6) through widespread stimulation of pattern recognition receptors (PRRs) by the release of danger stimuli, such as damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). DAMPs and PAMPs function as potent stimulators for host and donor-derived antigen presenting cells (APCs) that in turn activate and amplify the responses of alloreactive donor T cells. Emerging data also point towards a role for suppression of DAMP induced inflammation by the APCs and donor T cells in mitigating GVHD severity. In this review, we summarize the current understanding on the role of danger stimuli, such as the DAMPs and PAMPs, in GVHD.
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