Innate Immunity: Complement and Beyond

摘要 请求支助题为《先天免疫：补充和超越》的Keystone专题讨论会 由Claudia Kemper博士、Christoph Binder博士和冯绍博士组织。会议将在#年举行 雪鸟，犹他州，2022年4月3日至6日。 先天免疫力是宿主抵御感染和有害自我的支柱。病原体或危险 识别系统(PRR)，包括Toll样受体(TLRs)、炎症体和维甲酸诱导 基因I(rig-I)样受体被广泛认为是先天性免疫反应的中枢节点，具有 是免疫力研究的主要内容。然而，补语系统通常唤起的作用要小得多 对研究的热情，尽管从进化的角度来看是最古老的PRR。然而，这种观点是 变化；虽然补体系统曾经被视为仅仅是一种溶解的病原体杀手，但现在它被认识到 作为正常细胞生理的活跃的细胞内协调者。这一点，再加上意识到一个 越来越多的人类疾病，甚至新冠肺炎，涉及补体紊乱，已经刺激了 重新激发了人们对补体生物学及其治疗靶点的兴趣。然而，我们对如何 补体发挥非规范的活动，它如何与其他PRR相交是稀少的。这个基石 专题讨论会将及时介绍最近我们对 补体/PRR诱导的免疫，特别关注基本细胞过程中新出现的角色 包括染色质结构的调节、新陈代谢、细胞死亡、细胞碎片/身体的清除以及 维持正常的中枢神经系统功能。第二个重点是探索这些新的PRR的异常功能是如何 活动有助于感染和自身免疫，但也会导致不太直观的临床情况，如 认知和行为。这一关于PRR生物学的整体和包括补充性的优势点汇集在一起 来自学术界和工业界的跨学科研究人员，致力于新思想和新思想的交叉培养 在生物医学进步方面的合作与人类疾病的防治相辅相成。

ABSTRACT Support is requested for a Keystone Symposia conference entitled Innate Immunity: Complement and Beyond organized by Drs. Claudia Kemper, Christoph Binder and Feng Shao. The conference will be held in Snowbird, Utah from April 3-6, 2022. Innate immunity is a pillar of the host’s defense against infection and noxious self. Pathogen or danger recognition systems (PRRs) including toll-like receptors (TLRs), inflammasomes, and retinoic acid-inducible gene I (RIG-I) like receptors are broadly recognized as central nodes of innate immune responses and have been staples of immunity research. The complement system, however, generally evokes much less enthusiasm in research, despite being the oldest PRR from an evolutionary perspective. Yet, this view is changing; while the complement system was once viewed as a mere lytic pathogen-killer, it is now recognized as an active intracellular orchestrator of normal cell physiology. This, together with the realization that an increasing number of human diseases, even COVID-19, involve complement perturbations, has spurred a reinvigorated interest in complement biology and its therapeutic targeting. However, our knowledge of how complement exerts non-canonical activities and how it intersects with other PRRs is sparse. This Keystone Symposia conference will provide a timely account of recent paradigm shifts in our understanding of complement/PRR-instructed immunity with a specific eye on emerging roles in basic cellular processes including regulation of chromatin structure, metabolism, cell death, clearance of cellular debris/corpses, and maintenance of normal CNS function. A second focus is on exploring how aberrant function of these new PRR activities contribute to infection and autoimmunity but also to less intuitive clinical conditions like changes in cognition and behavior. This holistic and ‘complement-inclusive’ vantage-point on PRR biology brings together interdisciplinary investigators from academia and industry for cross-fertilization of novel ideas and collaborations towards biomedical progress in harnessing complement to combat human disease.