Hla-G

Carosella, Edgardo D.; Rouas‐Freiss, Nathalie; Roux, Diana Tronik‐Le; Moreau, Philippe; LeMaoult, Joël

doi:10.1016/bs.ai.2015.04.001

Cited by 335 publications

(199 citation statements)

References 457 publications

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“…In particular, genetic variations in these regions can modify interactions with cellular endogenous factors such as RNA-binding proteins and microRNAs [40]. It is noteworthy that in pathological situations where HLA-G is critical to control the patient’s immune system, the magnitude of HLA-G expression may vary depending on the individual [4] [41]. Although there is evidence that HLA-G 5’URR polymorphisms may influence the levels of promoter activity [42], investigations into the global impact of 3’UTR polymorphisms are lacking.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to normal conditions in which the expression of HLA-G is very restricted to few tissues, ectopic HLA-G expression is common in pathological situations such as cancer, and favors the tumor escape from the patient’s immune surveillance. In the case of transplantation, HLA-G favors the acceptance of allografts [4]. It is noteworthy that the levels of HLA-G expression vary across individuals [5], suggesting that the 53 identified HLA-G alleles (IPD-IMGT/HLA database, version 3.24.0.1), and their associated regulatory regions might respond to a specific microenvironment differentially.…”

Section: Introductionmentioning

confidence: 99%

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Haplotypes of the HLA-G 3’ Untranslated Region Respond to Endogenous Factors of HLA-G+ and HLA-G- Cell Lines Differentially

et al. 2017

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The immune checkpoint HLA-G prevents maternal rejection of the fetus and contributes in cancer invasion and acceptance of allografts. The 5’ and 3’ regulatory regions of the HLA-G gene are polymorphic and balancing selection probably maintains this variability. It is proposed that nucleotide variations may affect the level of HLA-G expression. To investigate this issue we aimed to analyze how haplotypes of the 3’ untranslated region (3’UTR) with highest worldwide frequencies, namely UTR-1, UTR-2, UTR-3, UTR-4, UTR-5, UTR-18 and UTR-7, impact the expression of a luciferase reporter gene in vitro. Experiments performed with the HLA-G positive cell lines JEG-3 (choricarcinoma) and FON (melanoma), and with the HLA-G negative cell lines M8 (melanoma) and U251MG (glioblastoma) showed that the HLA-G 3’UTR polymorphism influences the response to endogenous cellular factors and may vary according to the cell type. UTR-5 and UTR-7 impact the activity of luciferase the most whereas UTR-2, UTR-3, UTR-4, and UTR-18 have intermediate impact, and UTR-1 has the lowest impact. These results corroborate the previous associations between amounts of plasma sHLA-G levels and 3’UTR haplotypes in healthy individuals and reinforce that 3’UTR typing may be a predictor of the genetic predisposition of an individual to express different levels of HLA-G.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Haplotypes of the HLA-G 3’ Untranslated Region Respond to Endogenous Factors of HLA-G+ and HLA-G- Cell Lines Differentially

et al. 2017

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“…However, the most intriguing characteristic of this non-classical gene is its ability to form soluble as well as membrane-bound protein as a result of alternative splicing. A total of four membrane-bound and three soluble isoforms differ with respect to their size, structure, and ability to bind β2 microglobulin 67, 68 . The transcriptional regulation of HLA-G is complex and includes, but is not limited to, genetic variation within the 5’ and the 3’ UTRs 69– 71 .…”

Section: The Role For Major Histocompatibility Complex Resident Non-hmentioning

confidence: 99%

Role of major histocompatibility complex variation in graft-versus-host disease after hematopoietic cell transplantation

Petersdorf

2017

F1000Res

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Graft-versus-host disease (GVHD) remains a significant potentially life-threatening complication of allogeneic hematopoietic cell transplantation (HCT). Since the discovery of the human leukocyte antigen (HLA) system over 50 years ago, significant advances have clarified the nature of HLA variation between transplant recipients and donors as a chief etiology of GVHD. New information on coding and non-coding gene variation and GVHD risk provides clinicians with options to consider selected mismatched donors when matched donors are not available. These advances have increased the availability of unrelated donors for patients in need of a transplant and have lowered the overall morbidity and mortality of HCT.

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“…Our data demonstrates and re-confirms that HLA-G inhibits NK cell proliferation and cytotoxic activity through ILT2. Recent studies have considered HLA-G/ILT was an important immunological target, and that this is as important as B7/CTLA-4 and PD-L1/PD-1 in tumor immunotherapy [51, 67]. This study provides a theoretical basis for the participation of HLA-G in the immune escape of GC, and provides a new strategy for the immunotherapy of GC using HLA-G as the main target.…”

Section: Resultsmentioning

confidence: 91%

“…At present, there are two types of HLA-G inhibitory receptors associated with NK cells: immunoglobulin-like transcripts 2, ILT2 (CD85j/LILRB1); killer cell immunoglobulin-like receptors 2DL4, KIR2DL4 (CD158d). ILT2 is mainly expressed in monocytes, macrophages, dendritic cells, B cells, and in some T cells and NK cells; while KIR2DL4 is mainly expressed in uterine NK cells [50, 51]. The intracellular domain of ILT2 contains four immunoreceptor tyrosine-type inhibition motifs (ITIMs), which can transmit inhibitory signals into cells and inhibit the activity of immune cells.…”

Section: Discussionmentioning

confidence: 99%

Human Leukocyte Antigen-G Inhibits the Anti-Tumor Effect of Natural Killer Cells via Immunoglobulin-Like Transcript 2 in Gastric Cancer

Wan

Wang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Human leukocyte antigen-G (HLA-G) plays an important role in inhibiting natural killer (NK) cell function and promoting immune escape. However, the specific mechanism of HLA-G on NK in gastric cancer (GC) remains not well understood. This study investigated the expression of HLA-G in GC and the role of HLA-G-effected NK cells in GC progression. Methods: HLA-G expression in GC tissues obtained from 49 patients with GC was analyzed by immunohistochemistry and western blot. The number of tumor-infiltrating NK cells and the expression of their surface receptors were analyzed by immunohistochemistry and flow cytometry, respectively. The effect of HLA-G on NK cell proliferation was examined by Cell Counting Kit-8 (CCK8) assay. LDH release assay was used to evaluate the effect of HLA-G on the cytotoxic activity of NK cells, and the levels of IFN-γ and TNF-α in the co-cultured supernatant were detected by ELISA. Mice bearing a xenograft tumor model were used to examine the effect of HLA-G on the anti-tumor effect of NK cells. Results: HLA-G positive expression was detected in most of the GC tissues, and was correlated with the adverse prognosis of the disease. The expression of HLA-G was negatively associated with the number of tumor-infiltrating NK cells. Furthermore, GC cell lines with overexpressed HLA-G revealed their ability to inhibit the cell proliferation and cytotoxic activity of NK-92MI cells, and reduce the secretion of IFN-γ and TNF-α through immunoglobulin-like transcript 2 (ILT2). Finally, this in vivo experiment was able to prove that HLA-G can inhibit the anti-tumor effect of NK cells through ILT2. Conclusion: The expression of HLA-G was strongly correlated with the adverse prognosis of GC. The reason may be that it inhibits the proliferation and cytotoxic activity of infiltrating NK cells through ILT2.

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Hla-G

Cited by 335 publications

References 457 publications

Haplotypes of the HLA-G 3’ Untranslated Region Respond to Endogenous Factors of HLA-G+ and HLA-G- Cell Lines Differentially

Haplotypes of the HLA-G 3’ Untranslated Region Respond to Endogenous Factors of HLA-G+ and HLA-G- Cell Lines Differentially

Role of major histocompatibility complex variation in graft-versus-host disease after hematopoietic cell transplantation

Human Leukocyte Antigen-G Inhibits the Anti-Tumor Effect of Natural Killer Cells via Immunoglobulin-Like Transcript 2 in Gastric Cancer

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