Abstract:
:Cellular metabolism is dynamically regulated in NK cells and strongly influences their responses. Metabolic dysfunction is linked to defective NK cell responses in diseases such as obesity and cancer. The transcription factors, sterol regulatory element binding protein (SREBP) and cMyc, are crucial for controlling NK cell metabolic and functional responses, though the mechanisms involved are not fully understood. This study reveals a new role for SREBP in NK cells in supporting de novo polyamine synthesis through facilitating elevated cMyc expression. Polyamines have diverse roles and their de novo synthesis is required for NK cell glycolytic and oxidative metabolism and to support optimal NK cell effector functions. When NK cells with impaired SREBP activity were supplemented with exogenous polyamines, NK cell metabolic defects were not rescued but these NK cells displayed significant improvement in some effector functions. One role for polyamines is in the control of protein translation where spermidine supports the posttranslational hypusination of translation factor eIF5a. Pharmacological inhibition of hypusination also impacts upon NK cell metabolism and effector function. Considering recent evidence that cholesterol-rich tumor microenvironments inhibit SREBP activation and drive lymphocyte dysfunction, this study provides key mechanistic insight into this tumor-evasion strategy.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
O'Brien KL,Assmann N,O'Connor E,Keane C,Walls J,Choi C,Oefner PJ,Gardiner CM,Dettmer K,Finlay DKdoi
10.1002/eji.202048784subject
Has Abstractpub_date
2020-09-18 00:00:00eissn
0014-2980issn
1521-4141pub_type
杂志文章abstract::Cell suspensions enriched for N cells, the effector cell for human natural cell-mediated cytotoxicity, were observed to react strongly with a rabbit antiserum directed against an antigen associated with B cells. Treatment of the effector suspension with the antiserum resulted in inhibition of natural cell-mediated cyt...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830071016
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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doi:10.1002/eji.1830110510
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830111020
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journal_title:European journal of immunology
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830250636
更新日期:1995-06-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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doi:10.1002/1521-4141(2000012)30:12<3507::AID-IMMU3507
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abstract::The protooncogene HER2/neu encodes a 185-kDa transmembrane protein with extensive homology to the epidermal growth factor receptor. It is overexpressed in several human cancers of epithelial origin, such as pancreatic cancer. Previously, we demonstrated that cytotoxic T lymphocytes (CTL) derived from breast, ovarian, ...
journal_title:European journal of immunology
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doi:10.1002/eji.1830270511
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830260938
更新日期:1996-09-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830220604
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830120809
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journal_title:European journal of immunology
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doi:10.1002/eji.1830260712
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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abstract::Chlamydia pneumoniae stimulates potently maturation of and cytokine secretion by bone marrow-derived dendritic cells (BMDDC). BMDDC responses depend mainly on Toll-like receptor (TLR)2 and to a minor extent on TLR4. We demonstrate here using C. pneumoniae in an infectious model with the replication-permissive epitheli...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200209)32:9<2460::AID-IMMU2460>3
更新日期:2002-09-01 00:00:00
abstract::Using a new mAb, 2F1, we characterize a mouse natural killer (NK) cell antigen termed 'killer cell lectin-like receptor G1' (KLRG1; formerly mouse MAFA or 2F1-Ag). KLRG1 is expressed on 30-60% of murine NK cells, and a small fraction of T cells, and is composed of a homodimer of glycosylated 30-38-kDa subunits. Striki...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200003)30:3<920::AID-IMMU920>3.0
更新日期:2000-03-01 00:00:00
abstract::Treatment of systemic lupus erythematosus patients with epratuzumab (Emab), a humanized monoclonal antibody targeting CD22, leads to moderately reduced B-cell numbers but does not completely deplete B cells. Emab appears to induce immunomodulation of B cells, but the exact mode of action has not been defined. In the p...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201646383
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journal_title:European journal of immunology
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830211122
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201343718
更新日期:2014-01-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830270923
更新日期:1997-09-01 00:00:00
abstract::Foxp3-expressing Tregs play a non-redundant role in protecting against immune pathologies. Foxp3(+) Tregs can arise intra- and extra-thymically, however, the signals directing their differentiation and maintenance in the periphery are not well understood. We show that stimulation of mouse naïve CD4(+) T cells in vitro...
journal_title:European journal of immunology
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更新日期:2011-05-01 00:00:00