4,213 research outputs found
HLA-G and inflammatory diseases.
HLA-G antigens are non classical HLA-class I molecules characterized by a low allelic polymorphism, a limited tissue distribution and the presence of membrane bound and soluble isoforms. The HLA-G antigens were firstly detected in cytotrophoblast cells at the feto-maternal interface where they maintain a tolerogenic status between the mother and the semiallogenic fetus. Recently a variable expression of HLA-G molecules has been documented in several autoimmune diseases, viral infections, cancer diseases and transplantation. Overall the presence of HLA-G molecules in both membranes bound and soluble isoforms was associated with tolerogenic functions against innate and adaptative cellular responses. HLA-G antigens are able to affect the cytotoxicity of natural killer and CD8+ T cells, CD4+ T lymphocyte functions and dendritic cell maturation. In addition to the allelic polymorphism the HLA-G gene shows a deletion/insertion polymorphism of a 14 base pairs sequence (14bp) in the exon 8 at the 3’ untranslated region. Several reports have associated the presence of the 14bp insertion allele (+14bp) to an unstable mRNA and a lower sHLA-G protein production, suggesting a different ability to counteract inflammation between genotypes. We reviewed the literature on the expression of HLA-G antigens in autoimmune and allergic diseases and the possible functional role of these molecules in counteracting inflammation
Comment on "Experimental extracorporeal photopheresis inhibits the sensitization and effector phases of contact hypersensitivity via two mechanisms: Generation of IL-10 and induction of regulatory T cells"
Letter to the Editor on the paper by paper by Maeda and
coauthors (Experimental Extracorporeal Photopheresis Inhibits the Sensitization and Effector Phases of Contact Hypersensitivity via Two Mechanisms: Generation of IL-10 and Induction of Regulatory T Cells. J Immunol 2008; 181:5956-5962
HLA-G expression is a fundamental prerequisite to pregnancy
HLA-G antigens are thought to play a key role in implantation by controlling trophoblasts invasion and maintaining a local immunosuppressive state. The secretion of soluble HLA-G antigens (sHLA-G) by early embryos seems necessary for a successful implantation and could be a marker of increased pregnancy rate following in vitro fertilization. We have reviewed the results obtained during the last years. They overall confirmed the predictive role of sHLA-G production in pregnancy outcome. Furthermore, we have examined the technical procedures utilized with a particular attention to the monoclonal antibodies employed in the ELISA techniques.
New functional roles for HLA-G molecules in pregnancy could be suggested by the relationship observed between the presence of sHLA-G antigens in follicular fluids and sHLA-G expression in the corresponding fertilized oocyte. Furthermore, since maternal mRNA is fundamental for proteins production in early embryos, the biological role of the HLA-G 14bp polymorphism could be explored
The possible role of HLA-G molecules in human oocyte/embryo secretome
Human leucocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule observed for the first time in human cytotrophoblast. Several investigations have demonstrated the presence of soluble HLA-G in oocyte/embryo secretome. A focus on the possible role of HLA-G in oocyte/embryo context will be developed in this review. In addition, the possible use of HLA-G in assisted reproductive technology will be treated
Polymorphism in the 5' upstream regulatory and 3' untranslated regions of the HLA-G gene in relation to soluble HLA-G and IL-10 expression
The nonclassical human leukocyte antigen (HLA) class Ib gene HLA-G may be important for the induction and maintenance of immune tolerance between the mother and the semi-allogeneic fetus during pregnancy. Expression of HLA-G can influence cytokine and cytotoxic T-lymphocyte responses. Different HLA-G mRNA isoform expression patterns have been associated with HLA-G polymorphism, especially with a 14-bp insertion deletion polymorphism in the 3′ untranslated region (3′UTR) of the HLA-G gene. A significantly high level of interleukin-10 (IL-10) secretion is observed in homozygous +14/+14-bp HLA-G peripheral blood mononuclear cells after lipopolysaccharide (LPS) stimulation. This study finds that polymorphism in the 5′ upstream regulatory region (5′URR) of the HLA-G gene may also be implicated in differences in IL-10 secretion. However, this may also be due to linkage disequilibrium with the 14-bp polymorphism. A single-nucleotide polymorphism located −477 bp from the start site of exon 1 had a significant association with IL-10 concentrations but not after correction (p = 0.011; pc = 0.154). This polymorphism is located next to a heat shock element. Eighteen 5′-URR/3′-UTR HLA-G haplotypes were defined; one common homozygous genotype based on these haplotypes was significantly associated with a high IL-10 level after LPS stimulation compared to certain other genotypes. This study indicates that polymorphism in the 5′-URR of the HLA-G gene may have functional significance, although a new line of investigations is needed to elucidate these findings
Reduced production of anti-inflammatory soluble HLA-G molecules in styrene exposed workers
HLA-G antigens are non classical HLA-class I anti-inflammatory molecules. Since styrene exposure has been suggested to induce immune alteration, we analyzed plasma levels and “in vitro” peripheral blood mononuclear cell (PBMC) production of soluble HLA-G (sHLA-G) and Interleukin-10 (IL-10) molecules after lypopolysaccharide (LPS) stimulation, in styrene exposed workers and healthy subjects. Exposed workers showed reduced plasmatic levels of sHLA-G and IL-10 in comparison to healthy controls. Similarly, lower levels of sHLA-G and IL-10 molecules were observed in PBMC culture supernatants after LPS activation. These data propose styrene exposition as a mediator of an impaired sHLA-G production
Concentrazione di HLA-G solubile e interleuchina 10 nel plasma di pazienti psoriasici: possibile correlazione tra stato immunitario sistemico, trattamenti e malattia.
Si presentano i dati di una ricerca condotta su pazienti psoriasici, al fine di valutare l'eventuale correlazione tra livelli plasmatici di HLA-G e IL-10, quadro clutaneo e terapia. Il riscontro negli psoriasici di livelli di sHLA-G inferiori a quelli attesi, suggerisce il potenziale ruolo di questo antigene di istocompatibilità nell'espressione clinica della malattia. Si ipotizza peraltro il ruolo dei trattamenti sistemici immunomodulanti nella terapia della psoriasi anche attraverso l'innalzamento dei livelli sierici di HLA-G
Production of solubile HLA-G antigens by bone marrow - derived human mesenchimal cells (B-MSCS) has a role in the inhibition of the lymphoproliferative response.
Allergic women have reduced sHLA-G plasma levels at delivery
Problem
HLA-G antigen maintains a tolerogenic condition at the feto-maternal interface, counteracts inflammation in autoimmune diseases and soluble HLA-G (sHLA-G) levels decrease in allergic-asthmatics. Taking into consideration these findings we analyzed if sHLA-G and IL-10 could be influenced by pregnancy and labour in allergic and non-allergic women.
Method of Study
sHLA-G isoforms and interleukin 10 (IL-10) levels were determined in the plasma samples of 43 women (15 non-allergic, 28 allergic) during third trimester, at delivery and 2 years after pregnancy by immunoenzymatic assays.
Results
A significant increase in sHLA-G and IL-10 levels was documented at delivery in both allergic and non-allergic women. Allergic women showed lower sHLA-G concentrations. sHLA-G1 was evidenced as the predominant plasma isoform.
Conclusions
The data propose an impressive boost in sHLA-G and IL-10 concentrations at delivery, regardless of the allergic status. The sHLA-G1 isoform is the main responsible for the increased sHLA-G levels at delivery
The HLA-G genotype is associated with IL-10 levels in activated PBMCs
Human leukocyte antigen (HLA)-G is an MHC class Ib molecule that is expressed at the feto-maternal interface during pregnancy. However, recent results have also shown that it may have important functions as an immuno-modulatory factor in adult life. Differences in the pattern of alternative splicing and in the stability of HLA-G mRNA transcripts have been associated with HLA-G polymorphisms, especially a 14 bp deletion/insertion polymorphism in the 3' untranslated region of the HLA-G gene. We have investigated the secretion of HLA-G5/soluble HLA-G1 and interleukin-10 (IL-10) in lipopolysaccharide (LPS)-activated peripheral blood mononuclear lymphocytes (PBMCs) in relation to the HLA-G 14 bp genotype. No HLA-G5/sHLA-G1 could be detected in the non-activated control PBMC culture media, and there were no significant differences among the three HLA-G 14 bp genotypes regarding IL-10 concentrations. In LPS-activated PBMC cultures, no significant differences among the three HLA-G 14 bp genotypes regarding HLA-G5/sHLA-G1 concentrations were observed. However, this was in contrast to the IL-10 levels (P=0.0004, Kruskal-Wallis test). The +14/+14 bp PBMC samples expressed higher levels of IL-10 when compared to the -14/+14 bp genotype and the -14/-14 bp genotype. Interestingly, the IL-10 G/G polymorphism at position -1082 was more frequent in the +14/+14 bp genotype (P=0.024, chi2 test). These results support an autocrine loop between HLA-G5/sHLA-G1 and IL-10 expression in activated PBMCs, which may result in higher IL-10 levels in +14/+14 bp HLA-G genotypes
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