Innate Immunity: Complement and Beyond

摘要 请求为题为“先天免疫：补充和超越”的Keystone专题讨论会会议提供支助 由Claudia Kemper，Christoph Binder和Feng Shao博士组织。会议将于 2022年4月3日至6日，犹他州雪鸟。 先天免疫是宿主防御感染和有害自我的支柱。病原体或危险 识别系统（PRRs），包括Toll样受体（TLR）、炎性小体和视黄酸诱导的 基因I（RIG-I）样受体被广泛认为是先天免疫应答的中心节点， 成为免疫研究的斯台普斯。然而，补体系统通常引起的反应要少得多。 尽管从进化的角度来看，它是最古老的PRR，但它对研究充满热情。然而，这种观点是 虽然补体系统曾经被认为是一个纯粹的溶解性病原体杀手，但现在已经认识到， 作为正常细胞生理的活跃细胞内协调者。这一点，加上认识到， 越来越多的人类疾病，甚至是COVID-19，涉及补体干扰，已经刺激了一个 重振了对补体生物学及其治疗靶向的兴趣。然而，我们对 补体发挥非典型的活动，它如何与其他PRR相交是稀疏的。这个Keystone 专题讨论会将提供一个及时的帐户，最近的范式转变，我们的理解， 补体/PRR指导的免疫，特别关注基本细胞过程中的新兴作用 包括调节染色质结构、代谢、细胞死亡、清除细胞碎片/尸体，以及 维持正常的CNS功能。第二个重点是探索这些新的PRR的异常功能是如何发生的。 活动导致感染和自身免疫，但也导致不太直观的临床状况，如 认知和行为。PRR生物学的这种整体性和“互补性”优势点汇集了 来自学术界和工业界的跨学科研究人员， 在利用补体对抗人类疾病方面，为生物医学进步开展合作。

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.