Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-097 Warsaw, Poland.
Int J Mol Sci. 2022 Jul 23;23(15):8129. doi: 10.3390/ijms23158129.
Inflammasomes are intracellular multimeric complexes that cleave the precursors of the IL-1 family of cytokines and various proteins, found predominantly in cells of hematopoietic origin. They consist of pattern-recognition receptors, adaptor domains, and the enzymatic caspase-1 domain. Inflammasomes become activated upon stimulation by various exogenous and endogenous agents, subsequently promoting and enhancing inflammatory responses. To date, their function has been associated with numerous pathologies. Most recently, many studies have focused on inflammasomes' contribution to hematological diseases. Due to aberrant expression levels, NLRP3, NLRP1, and NLRC4 inflammasomes were indicated as predominantly involved. The NLRP3 inflammasome correlated with the pathogenesis of non-Hodgkin lymphomas, multiple myeloma, acute myeloid leukemia, lymphoid leukemias, myelodysplastic neoplasms, graft-versus-host-disease, and sickle cell anemia. The NLRP1 inflammasome was associated with myeloma and chronic myeloid leukemia, whereas NLRC4 was associated with hemophagocytic lymphohistiocytosis. Moreover, specific gene variants of the inflammasomes were linked to disease susceptibility. Despite the incomplete understanding of these correlations and the lack of definite conclusions regarding the therapeutic utility of inflammasome inhibitors, the available results provide a valuable basis for clinical applications and precede upcoming breakthroughs in the field of innovative treatments. This review summarizes the latest knowledge on inflammasomes in hematological diseases, indicates the potential limitations of the current research approaches, and presents future perspectives.
炎症小体是细胞内的多聚体复合物，可切割白细胞介素-1 家族细胞因子和各种蛋白的前体，主要存在于造血细胞中。它们由模式识别受体、衔接域和酶切半胱氨酸蛋白酶-1 结构域组成。炎症小体在受到各种外源性和内源性刺激物的刺激后被激活，随后促进和增强炎症反应。迄今为止，它们的功能已与许多病理相关。最近，许多研究集中在炎症小体对血液疾病的贡献上。由于异常表达水平，NLRP3、NLRP1 和 NLRC4 炎症小体被认为是主要涉及的。NLRP3 炎症小体与非霍奇金淋巴瘤、多发性骨髓瘤、急性髓系白血病、淋巴白血病、骨髓增生异常肿瘤、移植物抗宿主病和镰状细胞贫血的发病机制相关。NLRP1 炎症小体与骨髓瘤和慢性髓系白血病相关，而 NLRC4 与噬血细胞性淋巴组织细胞增多症相关。此外，炎症小体的特定基因变体与疾病易感性相关。尽管这些相关性的理解尚不完全，并且关于炎症小体抑制剂的治疗用途也没有明确的结论，但现有结果为临床应用提供了有价值的基础，并为创新治疗领域的即将突破提供了参考。本综述总结了炎症小体在血液疾病中的最新知识，指出了当前研究方法的潜在局限性，并提出了未来的展望。
