Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC, 27709, USA.
Oral and Craniofacial Biomedicine Curriculum, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Cell Death Differ. 2019 Jan;26(1):25-40. doi: 10.1038/s41418-018-0179-3. Epub 2018 Oct 22.
Compared to the tidy and immunologically silent death during apoptosis, necrosis seems like a chaotic and unorganized demise. However, we now recognize that there is a method to its madness, as many forms of necrotic cell death are indeed programmed and function beyond lytic cell death to support homeostasis and immunity. Inherently more immunogenic than their apoptotic counterpart, programmed necrosis, such as necroptosis, pyroptosis, ferroptosis, and NETosis, releases inflammatory cytokines and danger-associated molecular patterns (DAMPs), skewing the milieu to a pro-inflammatory state. Moreover, impaired clearance of dead cells often leads to inflammation. Importantly, these pathways have all been implicated in inflammatory and autoimmune diseases, therefore careful understanding of their molecular mechanisms can have long lasting effects on how we interpret their role in disease and how we translate these mechanisms into therapy.
与凋亡过程中整洁且免疫沉默的死亡相比，坏死似乎是一种混乱且无组织的死亡方式。然而，我们现在认识到，它的疯狂自有其道理，因为许多形式的坏死细胞死亡确实是有计划的，并通过裂解细胞死亡以外的方式发挥作用，以支持体内平衡和免疫。程序性坏死（如坏死性凋亡、细胞焦亡、铁死亡和 NETosis）比其凋亡对应物更具免疫原性，会释放炎症细胞因子和危险相关分子模式 (DAMPs)，使微环境偏向促炎状态。此外，清除死细胞的能力受损常常导致炎症。重要的是，这些途径都与炎症性和自身免疫性疾病有关，因此，仔细了解它们的分子机制可以对我们如何解释它们在疾病中的作用以及如何将这些机制转化为治疗方法产生持久影响。
