Apoptosis, necroptosis, and pyroptosis are genetically programmed cell death mechanisms that eliminate obsolete, damaged, infected, and self-reactive cells. Apoptosis fragments cells in a manner that limits immune cell activation, whereas the lytic death programs of necroptosis and pyroptosis release proinflammatory intracellular contents. Apoptosis fine-tunes tissue architecture during mammalian development, promotes tissue homeostasis, and is crucial for averting cancer and autoimmunity. All three cell death mechanisms are deployed to thwart the spread of pathogens. Disabling regulators of cell death signaling in mice has revealed how excessive cell death can fuel acute or chronic inflammation. Here we review strategies for modulating cell death in the context of disease. For example, BCL-2 inhibitor venetoclax, an inducer of apoptosis, is approved for the treatment of certain hematologic malignancies. By contrast, inhibition of RIPK1, NLRP3, GSDMD, or NINJ1 to limit proinflammatory cell death and/or the release of large proinflammatory molecules from dying cells may benefit patients with inflammatory diseases.

中文翻译：

---

健康和疾病中细胞死亡的控制


细胞凋亡、坏死性凋亡和细胞焦亡是基因编程的细胞死亡机制，可消除过时、受损、感染和自我反应的细胞。细胞凋亡以限制免疫细胞活化的方式碎片细胞，而坏死性凋亡和细胞焦亡的裂解性死亡程序释放促炎性细胞内内容物。细胞凋亡在哺乳动物发育过程中微调组织结构，促进组织稳态，对于避免癌症和自身免疫至关重要。所有三种细胞死亡机制都用于阻止病原体的传播。小鼠细胞死亡信号转导的禁用调节因子揭示了过度细胞死亡如何加剧急性或慢性炎症。在这里，我们回顾了在疾病背景下调节细胞死亡的策略。例如，BCL-2 抑制剂维奈托克（一种细胞凋亡诱导剂）被批准用于治疗某些血液系统恶性肿瘤。相比之下，抑制 RIPK1、NLRP3、GSDMD 或 NINJ1 以限制促炎细胞死亡和/或从垂死细胞中释放大促炎分子可能有益于炎症性疾病患者。