ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Upregulation of GRAIL is associated with impaired CD4 T cell proliferation in sepsis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- E3 ligase RNF128 restricts A. alternata-induced ILC2 activation and type 2 immune response in the murine lung.Scientific reports · 2025Article
- Lymphopenia in sepsis: a narrative review.Critical care (London, England) · 2024Review
- RNF128 regulates neutrophil infiltration and myeloperoxidase functions to prevent acute lung injury.Cell death & disease · 2023Article
- The Immunomodulatory Activity ofJournal of immunology research · 2023Article
- Recurrent Sepsis Exacerbates CD4Frontiers in immunology · 2021Article
- Extracellular CIRP induces macrophage endotoxin tolerance through IL-6R-mediated STAT3 activation.JCI insight · 2020Article
- Preexisting malignancy abrogates the beneficial effects of CXCR4 blockade during sepsis.Journal of leukocyte biology · 2020Article
- Ghrelin as an Anti-Sepsis Peptide: Review.Frontiers in immunology · 2020Review
- E3 Ubiquitin Ligases as Immunotherapeutic Target in Atherosclerotic Cardiovascular Disease.Frontiers in cardiovascular medicine · 2020Review
- Article
- Cold-inducible RNA-binding Protein Induces Neutrophil Extracellular Traps in the Lungs during Sepsis.Scientific reports · 2019Article
- Exendin-4 Exacerbates Burn-Induced Morbidity in Mice by Activation of the Sympathetic Nervous System.Mediators of inflammation · 2019Article
- CIRP increases ICAM-1Journal of leukocyte biology · 2018Article
- Macrophage expression of E3 ubiquitin ligase Grail protects mice from lipopolysaccharide-induced hyperinflammation and organ injury.PloS one · 2018Article
- The protective role of human ghrelin in sepsis: Restoration of CD4 T cell proliferation.PloS one · 2018Article
- B-1a Cells Protect Mice from Sepsis: Critical Role of CREB.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Desperate Times Call for Desperate Measures: Self-Cannibalism Is Protective During Sepsis.Critical care medicine · 2017Article
- GRAIL and Otubain-1 are Related to T Cell Hyporesponsiveness during Trypanosoma cruzi Infection.PLoS neglected tropical diseases · 2017Article
- Mannose-Capped Lipoarabinomannan from Mycobacterium tuberculosis Induces CD4+ T Cell Anergy via GRAIL.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Differential alterations of tissue T-cell subsets after sepsis.Immunology letters · 2015Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
The loss of numbers and functionality of CD4 T cells is observed in sepsis; however, the mechanism remains elusive. Gene related to anergy in lymphocytes (GRAIL) is critical for the impairment of CD4 T cell proliferation. We therefore sought to examine the role of GRAIL in CD4 T cell proliferation during sepsis. Sepsis was induced in 10-wk-old male C57BL/6 mice by cecal ligation and puncture. Splenocytes were isolated and subjected to flow cytometry to determine CD4 T cell contents. CD4 T cell proliferation was assessed by CFSE staining, and the expression of GRAIL in splenocytes was measured by immunohistochemistry, real-time PCR, and flow cytometry. The expressions of IL-2 and early growth response-2 were determined by real-time PCR. As compared with shams, the numbers of CD4 T cells were significantly reduced in spleens. Septic CD4 T cells were less efficient in proliferation than shams. The IL-2 expression was significantly reduced, whereas the GRAIL expression was significantly increased in septic mice splenocytes as compared with shams. The small interfering RNA-mediated knockdown of GRAIL expression re-established the CD4 T cell proliferation ability ex vivo. Similarly, the treatment with recombinant murine IL-2 to the septic CD4 T cells restored their proliferation ability by downregulating GRAIL expression. Our findings reveal a novel association of the increased GRAIL expression with impaired CD4 T cell proliferation, implicating an emerging therapeutic tool in sepsis.
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Registered trials
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