期刊
IMMUNOLOGICAL REVIEWS
卷 281, 期 1, 页码 115-123出版社
WILEY
DOI: 10.1111/imr.12607
关键词
Autoinflammation; Inflammasome; Inflammation; interleukin-18
类别
资金
- National Institute of Allergy and Infectious Diseases [K22AI123366, R01 AI088255]
- Richard King Mellon Foundation
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI088255, K22AI123366] Funding Source: NIH RePORTER
15 years ago, the fundamental biology of an inflammatory signaling complex eventually dubbed the inflammasome began to unravel in chronologic parallel with the discovery that many inflammatory diseases were associated with its hyperactivity. Though the genetic origins of Familial Mediterranean Fever (FMF, caused my mutations in MEFV) were discovered first, it would take nearly two decades before the mechanistic connections to a PYRIN inflammasome were made. In the interim, the intensive study of the NLRP3 inflammasome, and the diseases associated with its hyperactivation, have largely dictated the paradigm of inflammasome composition and function. Despite impressive gains, focusing on NLRP3 left gaps in our understanding of inflammasome biology. Foremost among these gaps were how inflammasomes become activated and the connections between inflammasome structure and function. Fortunately, work in another inflammasome inducer, NLRC4, grew to fill those gaps. The current understanding of the NLRC4 inflammasome is perhaps the most comprehensive illustration of the inflammasome paradigm: trigger (e.g. cytosolic flagellin), sensor (NAIP), nucleator (NLRC4), adaptor (ASC), and effector (CASP1). Detailed work has also identified observations that challenge this paradigm. Simultaneously, the features unique to each inflammasome offer a lesson in contrast, providing perspectives on inflammasome activation, regulation, and function. In this review, we endeavor to highlight recent breakthroughs related to NLRC4 inflammasome structure and activation, important in vivo work in infection and systemic inflammation, and the characterization of a spectrum of human NLRC4-associated autoinflammatory diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据