Journal article
iRhom2 Regulation of TACE Controls TNF-Mediated Protection Against Listeria and Responses to LPS
Science (American Association for the Advancement of Science), Vol.335(6065), pp.229-232
01/13/2012
DOI: 10.1126/science.1214448
PMCID: PMC4250273
PMID: 22246778
Abstract
Innate immune responses are vital for pathogen defense but can result in septic shock when excessive. A key mediator of septic shock is tumor necrosis factor–α (TNFα), which is shed from the plasma membrane after cleavage by the TNFα convertase (TACE). We report that the rhomboid family member iRhom2 interacted with TACE and regulated TNFα shedding. iRhom2 was critical for TACE maturation and trafficking to the cell surface in hematopoietic cells. Gene-targeted iRhom2-deficient mice showed reduced serum TNFα in response to lipopolysaccharide (LPS) and could survive a lethal LPS dose. Furthermore, iRhom2-deficient mice failed to control the replication of
Listeria monocytogenes
. Our study has identified iRhom2 as a regulator of innate immunity that may be an important target for modulating sepsis and pathogen defense.
Details
- Title: Subtitle
- iRhom2 Regulation of TACE Controls TNF-Mediated Protection Against Listeria and Responses to LPS
- Creators
- David R McIlwain - Campell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, CanadaPhilipp A Lang - Campell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, CanadaThorsten Maretzky - Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, NY 10021, USAKoichi Hamada - Okada Projects at the Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, JapanKazuhito Ohishi - Department of Pathology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, JapanSathish Kumar Maney - Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, GermanyThorsten Berger - Campell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, CanadaAditya Murthy - Ontario Cancer Institute, UHN, Toronto, Ontario, M5G 2M9, CanadaGordon Duncan - Campell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, CanadaHaifeng C Xu - Campell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, CanadaKarl S Lang - Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, GermanyDieter Häussinger - Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, GermanyAndrew Wakeham - Campell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, CanadaAnnick Itie-Youten - Campell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, CanadaRama Khokha - Ontario Cancer Institute, UHN, Toronto, Ontario, M5G 2M9, CanadaPamela S Ohashi - Campell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, CanadaCarl P Blobel - Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, NY 10021, USATak W Mak - Campell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, Canada
- Resource Type
- Journal article
- Publication Details
- Science (American Association for the Advancement of Science), Vol.335(6065), pp.229-232
- DOI
- 10.1126/science.1214448
- PMID
- 22246778
- PMCID
- PMC4250273
- NLM abbreviation
- Science
- ISSN
- 0036-8075
- eISSN
- 1095-9203
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: GM64750
- Language
- English
- Date published
- 01/13/2012
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984094309602771
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