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Ilt2 or lilrb1 or cd85j

Jérôme Rey, Cyril Fauriat, Eloïse Kochbati, Florence Orlanducci, Aude Charbonnier, Evelyne D'Incan, Pascale Andre, François Romagne, Bernadette Barbarat, Norbert Vey, Daniel Olive
NK cells are defective in acute myeloid leukemia (AML) at diagnosis. Here, we studied the kinetic of expression of the major activating and inhibitory receptors of NK, CD8 T, and γδ T cells in patients undergoing chemotherapy (CT) for the treatment of AML (n = 29). We showed that NK cells are the main affected population at diagnosis and that expression of activating receptors is partially restored within a few weeks after CT. CD8 T cells and γδ T cells are only weakly affected at diagnosis. Killer cell immunoglobulin-like receptor expression by NK cells, but not NKG2A and CD85j, was downregulated...
2017: Frontiers in Immunology
Sareetha Kailayangiri, Bianca Altvater, Christian Spurny, Silke Jamitzky, Sonja Schelhaas, Andreas H Jacobs, Constanze Wiek, Katharina Roellecke, Helmut Hanenberg, Wolfgang Hartmann, Heinz Wiendl, Susann Pankratz, Jutta Meltzer, Nicole Farwick, Lea Greune, Maike Fluegge, Claudia Rossig
Activated and in vitro expanded natural killer (NK) cells have substantial cytotoxicity against many tumor cells, but their in vivo efficacy to eliminate solid cancers is limited. Here, we used chimeric antigen receptors (CARs) to enhance the activity of NK cells against Ewing sarcomas (EwS) in a tumor antigen-specific manner. Expression of CARs directed against the ganglioside antigen GD2 in activated NK cells increased their responses to GD2+ allogeneic EwS cells in vitro and overcame resistance of individual cell lines to NK cell lysis...
2017: Oncoimmunology
Erick C Castelli, Petroula Gerasimou, Michelle A Paz, Jaqueline Ramalho, Iane O P Porto, Thálitta H A Lima, Andréia S Souza, Luciana C Veiga-Castelli, Cristhianna V A Collares, Eduardo A Donadi, Celso T Mendes-Junior, Paul Costeas
The HLA-G molecule presents immunomodulatory properties that might inhibit immune responses when interacting with specific Natural Killer and T cell receptors, such as KIR2DL4, ILT2 and ILT4. Thus, HLA-G might influence the outcome of situations in which fine immune system modulation is required, such as autoimmune diseases, transplants, cancer and pregnancy. The majority of the studies regarding the HLA-G gene variability so far was restricted to a specific gene segment (i.e., promoter, coding or 3' untranslated region), and was performed by using Sanger sequencing and probabilistic models to infer haplotypes...
March 2017: Molecular Immunology
Chen Chen, Jun Liang, Genhong Yao, Haifeng Chen, Bingyu Shi, Zhuoya Zhang, Cheng Zhao, Huayong Zhang, Lingyun Sun
BACKGROUND: Soluble human leukocyte antigen-G (sHLA-G) is a non-classical HLA class I molecule, exhibiting strong immunosuppressive properties by inducing the differentiation of T regulatory cells (Treg). Mesenchymal stem cells (MSCs) transplantation alleviates disease progression in systemic lupus erythematosus (SLE) patients. However, the underlying mechanisms are largely unknown. OBJECTIVES: To explore whether sHLA-G is involved in upregulating effects of MSCs on Treg, which contributes to therapeutic effects of MSCs transplantation in SLE...
January 24, 2017: International Immunopharmacology
Guillermo Juárez-Vega, Velia Rangel-Ramírez, Adriana Monsiváis-Urenda, Perla Niño-Moreno, Christian Garcia-Sepúlveda, Daniel E Noyola, Roberto González-Amaro
Human cytomegalovirus (HCMV) infection in children and young adults has been associated with changes in the innate immune system. We herein analyzed the possible effect of very long term HCMV infection on the expression of several NK cell receptors. Ninety HCMV-seropositive individuals were included and classified as young adults (n=30), elderly (n=30) and very elderly subjects (n=30). A peripheral blood sample was obtained and the expression of NK cell receptors (NKG2A, NKG2C, ILT2, CD161, KIR2DL1, KIR3DL1, and KIR3DL2) by NK and other lymphocyte subsets was assessed by flow cytometry...
March 2017: Human Immunology
L L Bi, Y Gao, Y J Sun, X R Kong, X Y He, X H Ma, W H Zhang, L Xiao, B Y Shi
Objective: To study the expression of membrane HLA-G (mHLA-G) and the receptor immunoglobulin-like transcript 2(ILT2) on lymphocyte and find their association with rejection and cytomegalovirus (CMV) infection after renal transplantation. Methods: A total of 88 cases of renal transplant recipients for the first time from February 2014 to February 2016 were studied in this work. Recipients can be divided into rejection group (n=12) and stable renal function group (n=41) according to whether rejection occurred...
January 10, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Yamila Sol Rocca, María Paula Roberti, Estefanía Paula Juliá, María Betina Pampena, Luisina Bruno, Sergio Rivero, Eduardo Huertas, Fernando Sánchez Loria, Alejandro Pairola, Anne Caignard, José Mordoh, Estrella Mariel Levy
The clinical outcome of colorectal cancer (CRC) is associated with the immune response; thus, these tumors could be responsive to different immune therapy approaches. Natural killer (NK) cells are key antitumor primary effectors that can eliminate CRC cells without prior immunization. We previously determined that NK cells from the local tumor environment of CRC tumors display a profoundly altered phenotype compared with circulating NK cells from healthy donors (HD). In this study, we evaluated peripheral blood NK cells from untreated patients and their possible role in metastasis progression...
2016: Frontiers in Immunology
X Xiao, J Hao, Y Wen, W Wang, X Guo, F Zhang
OBJECTIVES: The molecular mechanism of rheumatoid arthritis (RA) remains elusive. We conducted a protein-protein interaction network-based integrative analysis of genome-wide association studies (GWAS) and gene expression profiles of RA. METHODS: We first performed a dense search of RA-associated gene modules by integrating a large GWAS meta-analysis dataset (containing 5539 RA patients and 20 169 healthy controls), protein interaction network and gene expression profiles of RA synovium and peripheral blood mononuclear cells (PBMCs)...
July 2016: Bone & Joint Research
H Eguchi, A Maeda, P C Lo, R Matsuura, E L Esquivel, M Asada, R Sakai, K Nakahata, T Yamamichi, S Umeda, K Deguchi, T Ueno, H Okuyama, S Miyagawa
The inhibitory function of HLA-G1, a class Ib molecule, on monocyte/macrophage-mediated cytotoxicity was examined. The expression of inhibitory receptors that interact with HLA-G, immunoglobulin-like transcript 2 (ILT2), ILT4, and KIR2DL4 (CD158d) on in vitro-generated macrophages obtained from peripheral blood mononuclear cells and the phorbol 12-myristate 13-acetate (PMA)-activated THP-1 cells were examined by flow cytometry. cDNAs of HLA-G1, HLA-G3, HLA-E, and human β2-microglobulin were prepared, transfected into pig endothelial cells (PECs), and macrophage- and the THP-1 cell-mediated PEC cytolysis was then assessed...
May 2016: Transplantation Proceedings
Vera Rebmann, Lisa König, Fabiola da Silva Nardi, Bettina Wagner, Luis Felipe Santos Manvailer, Peter A Horn
The HLA-G molecule is a member of the non-classical HLA class I family. Its surface expression is physiologically restricted to the maternal-fetal interface and to immune privileged adult tissues. Despite the restricted tissue expression, HLA-G is detectable in body fluids as secreted soluble molecules. A unique feature of HLA-G is the structural diversity as surface expressed and as secreted molecules. Secreted HLA-G can be found in various body fluids either as free soluble HLA-G or as part of extracellular vesicles (EVs), which are composed of various antigens/ligands/receptors, bioactive lipids, cytokines, growth factors, and genetic information, such as mRNA and microRNA...
2016: Frontiers in Immunology
Christine Pasero, Gwenaëlle Gravis, Mathilde Guerin, Samuel Granjeaud, Jeanne Thomassin-Piana, Palma Rocchi, Maria Paciencia-Gros, Flora Poizat, Mélanie Bentobji, Francine Azario-Cheillan, Jochen Walz, Naji Salem, Serge Brunelle, Alessandro Moretta, Daniel Olive
The field of immunotherapy for solid tumors, such as prostate cancer, has been recently focusing on therapies that can counter tumor-mediated immunosuppression. Precise quantification and characterization of the immune infiltrates in tumors is crucial to improve treatment efficacy. Natural killer (NK) cells, major components of the antitumor immune system, have never been isolated from prostate tumors, despite their suspected role in disease progression. Here, we examined the frequency, phenotype, and functions of NK cells infiltrating control and tumor prostate tissues...
April 15, 2016: Cancer Research
Rahul C Khanolkar, Michail Kalogeropoulos, Alistair Lawrie, Ali Roghanian, Mark A Vickers, Neil T Young
Inhibitory receptors of the human leukocyte immunoglobulin-like receptor family are constitutively expressed on all myeloid cell types and regulate their functional activity. We demonstrate that ligation of the human leukocyte antigen class I-specific receptor LILRB1, during the differentiation of monocytes to dendritic cells in vitro, results in increased expression of the nuclear factor κB inhibitor protein ABIN1 (also known as TNIP1). Similarly increased expression of ABIN1/TNIP1 was observed in the "immunosuppressive" monocyte populations of patients with non-Hodgkin lymphoma ex vivo...
April 29, 2016: Journal of Leukocyte Biology
Diogo Baía, Jordi Pou, Des Jones, Ofer Mandelboim, John Trowsdale, Aura Muntasell, Miguel López-Botet
Leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) has been reported to interact with a wide spectrum of HLA class I (HLA-I) molecules, albeit with different affinities determined by allelic polymorphisms and conformational features. HLA-G dimerization and the presence of intracellular Cys residues in HLA-B7 have been shown to be critical for their recognition by LILRB1. We hypothesized that dimerization of classical HLA class Ia molecules, previously detected in exosomes, might enhance their interaction with LILRB1...
July 2016: European Journal of Immunology
Simon Jasinski-Bergner, Adi Reches, Christine Stoehr, Chiara Massa, Evamaria Gonschorek, Stefan Huettelmaier, Juliane Braun, Sven Wach, Bernd Wullich, Verena Spath, Ena Wang, Francesco M Marincola, Ofer Mandelboim, Arndt Hartmann, Barbara Seliger
The non-classical human leukocyte antigen G (HLA-G) is expressed at a high frequency in renal cell carcinoma (RCC) and is associated with a higher tumor grade and a poor clinical outcome. This might be caused by the HLA-G-mediated inhibition of the cytotoxicity of T and NK cells. Therefore a selective targeting of HLA-G might represent a powerful strategy to enhance the immunogenicity of RCC lesions. Recent studies identified a number of HLA-G-regulating microRNAs (miRs) and demonstrated an inverse expression of some of these miRs with HLA-G in RCC in vitro and in vivo...
May 3, 2016: Oncotarget
Aura Muntasell, Aldi Pupuleku, Elisa Cisneros, Andrea Vera, Manuela Moraru, Carlos Vilches, Miguel López-Botet
CD94/NKG2C and lack of FcεRγ (FcRγ) expression are considered markers of the adaptive NK cell response to human CMV (HCMV) infection. Despite the fact that FcRγ(-) and NKG2C(bright) NK cells share some phenotypic, epigenetic, and functional features, their relationship remains unclear. To address this issue, a systematic analysis of NKG2C(bright) and FcRγ expression was carried out in NK cells from a cohort of healthy young adults (n = 81) considering NKG2C copy number, previously related to the magnitude of NKG2C(+) NK cell expansion...
May 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Izabela Nowak, Andrzej Malinowski, Ewa Barcz, Jacek R Wilczyński, Marta Wagner, Edyta Majorczyk, Hanna Motak-Pochrzęst, Małgorzata Banasik, Piotr Kuśnierczyk
The KIR2DL4 receptor and its ligand HLA-G are considered important for fetal-maternal immune tolerance and successful pregnancy. The absence of a particular variant of KIR2DL4 might be a bad prognostic factor for pregnancy outcome. However, it could be compensated by the presence of the respective LILRB1 allele. Therefore, we investigated the KIR2DL4, LILRB1 and HLA-G polymorphisms in 277 couples with spontaneous abortion and 219 control couples by HRM, PCR-SSP and RFLP methods. We found a protective effect of women's heterozygosity in -716 HLA-G (p = 0...
December 2016: Archivum Immunologiae et Therapiae Experimentalis
Ching-Lien Wu, Signe Goul Svendsen, Adrien Riviere, François Desgrandchamps, Edgardo D Carosella, Joël LeMaoult
Human leukocyte antigen (HLA)-G is an immune-inhibitory molecule that exerts its function via interaction with two main inhibitory receptors: ILT2 and ILT4. This interaction is considered to be an immune checkpoint. HLA-G can be found as a soluble molecule, but it is not known if its receptors can also be found as soluble molecules. In this work, we present a multiplex luminex-based assay to measure soluble ILT2 (sILT2) and soluble ILT4 (sILT4) molecules together. It is based on two antibody pairs, GHI/75 and HP-F1-PE for ILT2 and 27D6 and 42D1-PE for ILT4...
September 2016: Human Immunology
Virginie Prod'homme, Peter Tomasec, Charles Cunningham, Marius K Lemberg, Richard J Stanton, Brian P McSharry, Eddie C Y Wang, Simone Cuff, Bruno Martoglio, Andrew J Davison, Véronique M Braud, Gavin W G Wilkinson
Human CMV (HCMV)-encoded NK cell-evasion functions include an MHC class I homolog (UL18) with high affinity for the leukocyte inhibitory receptor-1 (CD85j, ILT2, or LILRB1) and a signal peptide (SP(UL40)) that acts by upregulating cell surface expression of HLA-E. Detailed characterization of SP(UL40) revealed that the N-terminal 14 aa residues bestowed TAP-independent upregulation of HLA-E, whereas C region sequences delayed processing of SP(UL40) by a signal peptide peptidase-type intramembrane protease. Most significantly, the consensus HLA-E-binding epitope within SP(UL40) was shown to promote cell surface expression of both HLA-E and gpUL18...
March 15, 2012: Journal of Immunology: Official Journal of the American Association of Immunologists
Neil T Young, Edward C P Waller, Rashmi Patel, Ali Roghanian, Jonathan M Austyn, John Trowsdale
Dendritic cells (DCs) link innate and adaptive immunity, initiating and regulating effector cell responses. They ubiquitously express members of the LILR (ILT, LIR, CD85) family of molecules, some of which recognize self-HLA molecules, but little is known of their possible functions in DC biology. We demonstrate that the inhibitory receptor LILRB1 (ILT2, LIR1, CD85j) is selectively up-regulated during DC differentiation from monocyte precursors in culture. Continuous ligation of LILRB1 modulated cellular differentiation, conferred a unique phenotype upon the resultant cells, induced a profound resistance to CD95-mediated cell death, and inhibited secretion of cytokines IL-10, IL-12p70, and TGF-beta...
March 15, 2008: Blood
A Monsiváis-Urenda, P Niño-Moreno, C Abud-Mendoza, L Baranda, E Layseca-Espinosa, M López-Botet, R González-Amaro
The aim of this work was to study the expression and function of the inhibitory receptor ILT2/CD85j in peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE). We studied 23 SLE patients as well as 17 patients with rheumatoid arthritis, 10 with fibromyalgia, and 23 healthy individuals. We found a variable level of expression of ILT2 in the PBMC from both SLE patients and controls, with no significant differences among them. However, when the expression of this receptor was assessed in cell subsets, significantly lower levels were detected in CD19+ lymphocytes from SLE patients compared with healthy controls...
September 2007: Journal of Autoimmunity
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