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The Impact of NLRP3 Activation on Hematopoietic Stem Cell Transplantation

NLRP3激活對(duì)造血干細(xì)胞移植的影響

NLR family pyrin domain-containing 3 (NLRP3) is an intracellular protein that after recognizing a broad spectrum of stressors, such as microbial motifs and endogenous danger signals, promotes the activation and release of the pro-inflammatory cytokines IL-1β and IL-18, thus playing an essential role in the innate immune response. Several blood cell types, including macrophages, dendritic cells, and hematopoietic stem and progenitor cells (HSPCs), express NLRP3, where it has been implicated in various physiological and pathological processes. For example, NLRP3 participates in the development and expansion of HSPCs, and their release from bone marrow into the peripheral blood has been implicated in certain hematological disorders including various types of leukemia.

NLR 家族含 pyrin 結(jié)構(gòu)域 3 (NLRP3) 是一種細(xì)胞內(nèi)蛋白，在識(shí)別微生物基序和內(nèi)源性危險(xiǎn)信號(hào)等廣譜壓力源后，促進(jìn)促炎細(xì)胞因子 IL-1β 和 IL-18 的激活和釋放，從而在先天免疫反應(yīng)中發(fā)揮重要作用。幾種血細(xì)胞類型，包括巨噬細(xì)胞、樹突細(xì)胞和造血干細(xì)胞和祖細(xì)胞 (HSPC)，表達(dá) NLRP3，它與各種生理和病理過程有關(guān)。例如，NLRP3 參與 HSPC 的發(fā)育和擴(kuò)增，它們從骨髓釋放到外周血中與某些血液疾病包括各種類型的白血病有關(guān)。

 
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In addition, accumulating evidence indicates that activation of NLRP3 plays a pivotal role in the development of transplant complications in patients receiving hematopoietic stem cell transplantation (HSCT) including graft versus host disease, severe infections, and transplant-related mortality. The majority of these complications are triggered by the severe tissue damage derived from the conditioning regimens utilized in HSCT which, in turn, activates NLRP3 and, ultimately, promotes the release of proinflammatory cytokines such as IL-1β and IL-18. Here, we summarize the implications of NLRP3 in HSCT with an emphasis on the involvement of this inflammasome component in transplant complications.

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此外，越來越多的證據(jù)表明，NLRP3 的激活在接受造血干細(xì)胞移植 (HSCT) 的患者的移植并發(fā)癥的發(fā)展中起著關(guān)鍵作用，包括移植物抗宿主病、嚴(yán)重感染和移植相關(guān)死亡率。大多數(shù)這些并發(fā)癥是由 HSCT 中使用的預(yù)處理方案引起的嚴(yán)重組織損傷引發(fā)的，這反過來激活 NLRP3，并最終促進(jìn)促炎細(xì)胞因子的釋放，如 IL-1β 和 IL-18。在這里，我們總結(jié)了 NLRP3 在 HSCT 中的意義，重點(diǎn)是這種炎癥小體成分在移植并發(fā)癥中的參與。嚴(yán)重感染和移植相關(guān)死亡率。大多數(shù)這些并發(fā)癥是由 HSCT 中使用的預(yù)處理方案引起的嚴(yán)重組織損傷引發(fā)的，這反過來激活 NLRP3，并最終促進(jìn)促炎細(xì)胞因子的釋放，如 IL-1β 和 IL-18。在這里，我們總結(jié)了 NLRP3 在 HSCT 中的意義，重點(diǎn)是這種炎癥小體成分在移植并發(fā)癥中的參與。嚴(yán)重感染和移植相關(guān)死亡率。大多數(shù)這些并發(fā)癥是由 HSCT 中使用的預(yù)處理方案引起的嚴(yán)重組織損傷引發(fā)的，這反過來激活 NLRP3，并最終促進(jìn)促炎細(xì)胞因子的釋放，如 IL-1β 和 IL-18。在這里，我們總結(jié)了 NLRP3 在 HSCT 中的意義，重點(diǎn)是這種炎癥小體成分在移植并發(fā)癥中的參與。

來源：MDPI https://www.mdpi.com/1422-0067/22/21/11845