Publication Date:
2012-01-17
Description:
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-alpha (TNFalpha), which is shed from the plasma membrane after cleavage by the TNFalpha convertase (TACE). We report that the rhomboid family member iRhom2 interacted with TACE and regulated TNFalpha shedding. iRhom2 was critical for TACE maturation and trafficking to the cell surface in hematopoietic cells. Gene-targeted iRhom2-deficient mice showed reduced serum TNFalpha 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4250273/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4250273/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McIlwain, David R -- Lang, Philipp A -- Maretzky, Thorsten -- Hamada, Koichi -- Ohishi, Kazuhito -- Maney, Sathish Kumar -- Berger, Thorsten -- Murthy, Aditya -- Duncan, Gordon -- Xu, Haifeng C -- Lang, Karl S -- Haussinger, Dieter -- Wakeham, Andrew -- Itie-Youten, Annick -- Khokha, Rama -- Ohashi, Pamela S -- Blobel, Carl P -- Mak, Tak W -- GM64750/GM/NIGMS NIH HHS/ -- R01 GM064750/GM/NIGMS NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2012 Jan 13;335(6065):229-32. doi: 10.1126/science.1214448.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Campell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22246778" target="_blank"〉PubMed〈/a〉
Keywords:
ADAM Proteins/genetics/*metabolism
;
Amino Acid Sequence
;
Animals
;
B-Lymphocytes/immunology/metabolism
;
Base Sequence
;
Carrier Proteins/chemistry/genetics/*metabolism
;
Cell Line
;
Cell Membrane/metabolism
;
Gene Deletion
;
*Immunity, Innate
;
Lipopolysaccharides/*immunology
;
Listeria monocytogenes/immunology/physiology
;
Listeriosis/*immunology/metabolism/microbiology/pathology
;
Macrophages/immunology/metabolism
;
Macrophages, Peritoneal/immunology/metabolism/microbiology
;
Mice
;
Molecular Sequence Data
;
Protein Transport
;
Shock, Septic/*immunology/metabolism
;
Spleen/cytology
;
Tumor Necrosis Factor-alpha/blood/genetics/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
