Garg Vaishali, Chandanala Shashank, David-Luther M, Govind M, Prasad Roshni Ravi, Kumar Anujith, Prasanna S Jyothi
Manipal Institute of Regenerative Medicine, Manipal Academy of Higher Education (MAHE), Bangalore, India.
Front Cell Dev Biol. 2022 Feb 7;10:793694. doi: 10.3389/fcell.2022.793694. eCollection 2022.
The impact of immune system and inflammation on organ homeostasis and tissue stem cell niches in the absence of pathogen invasion has long remained a conundrum in the field of regenerative medicine. The paradoxical role of immune components in promoting tissue injury as well as resolving tissue damage has complicated therapeutic targeting of inflammation as a means to attain tissue homeostasis in degenerative disease contexts. This confound could be resolved by an integrated intricate assessment of cross-talk between inflammatory components and micro- and macro-environmental factors existing in tissues during health and disease. Prudent fate choice decisions of stem cells and their differentiated progeny are key to maintain tissue integrity and function. Stem cells have to exercise this fate choice in consultation with other tissue components. With this respect tissue immune components, danger/damage sensing molecules driving sterile inflammatory signaling cascades and barrier cells having immune-surveillance functions play pivotal roles in supervising stem cell decisions in their niches. Stem cells learn from their previous damage encounters, either endogenous or exogenous, or adapt to persistent micro-environmental changes to orchestrate their decisions. Thus understanding the communication networks between stem cells and immune system components is essential to comprehend stem cell decisions in endogenous tissue niches. Further the systemic interactions between tissue niches integrated through immune networks serve as patrolling systems to establish communication links and orchestrate micro-immune ecologies to better organismal response to injury and promote regeneration. Understanding these communication links is key to devise immune-centric regenerative therapies. Thus the present review is an integrated attempt to provide a unified purview of how inflammation and immune cells provide guidance to stem cells for tissue sculpting during development, organismal aging and tissue crisis based on the current knowledge in the field.
在没有病原体入侵的情况下，免疫系统和炎症对器官稳态及组织干细胞生态位的影响长期以来一直是再生医学领域的一个难题。免疫成分在促进组织损伤以及解决组织损伤方面所起的矛盾作用，使炎症作为在退行性疾病背景下实现组织稳态的一种手段的治疗靶点变得复杂。通过对健康和疾病状态下组织中炎症成分与微观和宏观环境因素之间的相互作用进行综合细致的评估，或许可以解决这一难题。干细胞及其分化后代做出谨慎的命运选择决定是维持组织完整性和功能的关键。干细胞必须与其他组织成分协商后做出这种命运选择。在这方面，组织免疫成分、驱动无菌炎症信号级联反应的危险/损伤传感分子以及具有免疫监视功能的屏障细胞在监督干细胞在其生态位中的决定方面发挥着关键作用。干细胞从其先前遇到的内源性或外源性损伤中学习，或适应持续的微环境变化来精心策划其决定。因此，了解干细胞与免疫系统成分之间的通信网络对于理解内源性组织生态位中的干细胞决定至关重要。此外，通过免疫网络整合的组织生态位之间的系统相互作用作为巡逻系统，建立通信联系并协调微免疫生态，以更好地使机体对损伤做出反应并促进再生。理解这些通信联系是设计以免疫为中心的再生疗法的关键。因此，本综述综合了当前该领域的知识，试图提供一个统一的视角，阐述炎症和免疫细胞如何在发育、机体衰老和组织危机期间为干细胞提供指导以进行组织塑造。
