Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/19589
Title: NLRP1 restricts butyrate producing commensals to exacerbate inflammatory bowel disease.
Authors: Tye, Hazel;Yu, Chien-Hsiung;Simms, Lisa A;de Zoete, Marcel R;Kim, Man Lyang;Zakrzewski, Martha;Penington, Jocelyn S;Harapas, Cassandra R;Souza-Fonseca-Guimaraes, Fernando;Wockner, Leesa F;Preaudet, Adele;Mielke, Lisa A;Wilcox, Stephen A;Ogura, Yasunori;Corr, Sinead C;Kanojia, Komal;Kouremenos, Konstantinos A;De Souza, David P;McConville, Malcolm J;Flavell, Richard A;Gerlic, Motti;Kile, Benjamin T;Papenfuss, Anthony T;Putoczki, Tracy L;Radford-Smith, Graham L;Masters, Seth L
Affiliation: Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Heidelberg, VIC, 3084, Australia
Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel
ACRF Chemical Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia
Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, 3800, VIC, Australia
Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, 3010, Australia
Bioinformatics and Cancer Genomics Lab, Peter MacCallum Cancer Centre, Melbourne, VIC, 3002, Australia
Department of Gastroenterology, Royal Brisbane and Women's Hospital, Brisbane, 4029, QLD, Australia
University of Queensland School of Medicine, Brisbane, 4029, QLD, Australia
Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia
Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia
Gut Health, QIMR Berghofer Medical Research Institute, Brisbane, 4029, QLD, Australia
Department of Immunobiology, Yale University School of Medicine, New Haven, CT, 06519, USA
Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, 3584 CL, The Netherlands
Medical Genomics, QIMR Berghofer Medical Research Institute, Brisbane, 4029, QLD, Australia
Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia
Molecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia
Statistics Division, QIMR Berghofer Medical Research Institute, Brisbane, 4029, QLD, Australia
Systems Biology and Personalized Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia
Department of Food Science and Nutrition, Nara Women's University, Nara, 6308506, Japan
Department of Microbiology, The Moyne Institute of Preventative Medicine, School of Genetics and Microbiology, Trinity College Dublin, Dublin 2, Ireland
Metabolomics Australia, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, VIC, 3010, Australia
Department of Biochemistry and Molecular Biology, Parkville, VIC, 3010, Australia
Howard Hughes Medical Institute, Yale University, New Haven, CT, 06510, USA
Issue Date: 13-Sep-2018
EDate: 2018-09-13
Citation: Nature communications 2018; 9(1): 3728
Abstract: Anti-microbial signaling pathways are normally triggered by innate immune receptors when detecting pathogenic microbes to provide protective immunity. Here we show that the inflammasome sensor Nlrp1 aggravates DSS-induced experimental mouse colitis by limiting beneficial, butyrate-producing Clostridiales in the gut. The colitis-protective effects of Nlrp1 deficiency are thus reversed by vancomycin treatment, but recapitulated with butyrate supplementation in wild-type mice. Moreover, an activating mutation in Nlrp1a increases IL-18 and IFNγ production, and decreases colonic butyrate to exacerbate colitis. We also show that, in patients with ulcerative colitis, increased NLRP1 in inflamed regions of the colon is associated with increased IFN-γ. In this context, NLRP1, IL-18 or IFN-γ expression negatively correlates with the abundance of Clostridiales in human rectal mucosal biopsies. Our data identify the NLRP1 inflammasome to be a key negative regulator of protective, butyrate-producing commensals, which therefore promotes inflammatory bowel disease.
URI: http://ahro.austin.org.au/austinjspui/handle/1/19589
DOI: 10.1038/s41467-018-06125-0
ORCID: 0000-0003-1561-0074
0000-0002-8921-9265
0000-0001-9518-1833
0000-0002-1102-8506
0000-0002-2047-6239
0000-0003-4763-576X
PubMed URL: 30214011
Type: Journal Article
Appears in Collections:Journal articles

Files in This Item:
There are no files associated with this item.


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.