Journal article

Mechanisms of NLRP1-Mediated Autoinflammatory Disease in Humans and Mice

Chien-Hsiung Yu, Jonas Moecking, Matthias Geyer, Seth L Masters

JOURNAL OF MOLECULAR BIOLOGY | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD | Published : 2018

Abstract

NLRP1 was the first NOD-like receptor described to form an inflammasome, recruiting ASC to activate caspase-1, which processes interleukin-1β and interleukin-18 to their active form. A wealth of new genetic information has now redefined our understanding of this innate immune sensor. Specifically, rare loss-of-function variants in the N-terminal pyrin domain indicate that this part of NLRP1 is autoinhibitory and normally acts to prevent a familial autoinflammatory skin disease associated with cancer. In the absence of a ligand to trigger human NLRP1, these mutations have now confirmed the requirement of NLRP1 autolytic cleavage within the FIIND domain, which had previously been implicated in..

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University of Melbourne Researchers

Grants

Awarded by Bonn & Melbourne Graduate School BoMeRanG


Awarded by Australian National Health and Medical Research Council


Funding Acknowledgements

C.-H.Y. is a recipient of WEHI Centenary Fellowship and Ormond College's Thwaites Gutch Fellowship in Physiology. J.M. is funded by the Bonn & Melbourne Graduate School Bo&MeRanG (GRK 2168). M.G. is a member of the DFG excellence cluster Immuno-Sensation. S.L.M. received funding from an Australian National Health and Medical Research Council project grant (1099262), the Viertel Foundation, and Glaxosmithkline. The authors declare no competing interests.