functional and molecular characterization of myeloid suppressor cells expanded during CORD-Papers-2021-10-25 (Version 1)

Title: Functional and Molecular Characterization of Myeloid Suppressor Cells Expanded During Lymphoma Tumour Progression
Abstract: We previously reported that in mice with large progressing Tcell lymphoma tumours, dysfunctions in the antitumour CTL activity occur, associated with an accumulation of splenic arginaseproducing myeloid suppressor cells (MSCs). In this study, we first demonstrate that both the presence and the activation state of these MSC depends on tumour evolution. While in tumour regressors hardly any arginaseproducing MSC can be found, both the amount and the arginase activity of this population expands from early over late progressors. This gradual induction of MSCs is paralleled by an increasing suppression of CTL activity and Th1, but not Th2, cytokine production. Upon analysing the molecular repertoire of MSC in vitro, we found, besides arginase1, a wellestablished marker for alternatively activated myeloid cells or M2, a strong upregulation of FIZZ1 and Ym, two additional recently identified markers for M2. Further evaluation of molecular markers by microarray analysis in MSC yielded genes involved in wound healing (e.g. coagulation factor XIIIa), antiinflammation (e.g. selenoprotein P), immunomodulation (e.g. PDL2) and fat and sugar metabolism (e.g. leptin receptor). Of note, many of these genes are regulated by type 2 cytokines (IL4, IL13 and IL10) and are therefore rather M2 associated. Overall, our data provide new markers for MSC in cancer and further establish their M2 activation state.
Published: 6/28/2008
Journal: Scand J Immunol
DOI: 10.1111/j.0300-9475.2004.01423bl.x
Author Name: Meerschaut, S
Author link:
Author Name: Liu, Y
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Author Name: Hassanzadeh, G H G
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Author Name: Raes, G
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Author Name: De Baetselier, P
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Author Name: Van Ginderachter, J
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sha: 81ca433af7177a1d42a56198e8e675e9fc3a68ea
license: no-cc
license_url: [no creative commons license associated]
source_x: PMC
pmcid: PMC7169586
has_full_text: TRUE
Keywords Extracted from Text Content: 4-colour marginal zone macrophages human gut flora-derived lactobacilli T-cell cultures CaCo-2 carbohydrate structures TNF-a PD-L2 ceramide hl60 protein-A Ab2 antibodies bacteria-derived antigens FHR-1 Heat Shock Protein 70 mMGL2 thymidine i.n hyperimmunized mice Trypanosoma cruzi interleukin 2 type I allergen MBP epithelial layers Natural Killer Cell FIZZ1 Annelida Type I IFN monocyte-derived dendritic cells costimulatory HbsAg-specific IgM HLA-Cw6 porcine cells CCF-induced macrophage Vitamin C ICOS lymphocytes IAPderived IgA1 V. parvula hepatocellular carcinoma IgA antibodies Cell vascular endothelium H. mammalian cell non-NK lineage-specific antibodies Veillonella parvula mast cell B7.1 citrullin vitamin E C5a anaphylatoxins IL-5 CD25 IAP 18:213-25 PBMCs cancer fibrin human NK cells AM Plasmodium falciparum HSP70 cancers Oligochaeta Th-cell TGF-b salivary gland tissue NO intercellular contact HDM MT2/MT1 spleen fluticasone propionate low-QBC Type I Interferon B-chains ASMase anti-Lactobacillus antibodies HDM extracts Macrophage Galactose-Type C-Type Lectins 1 YadA KB-cell line liver X receptors Pneumococci SCRs 18-20 of factor H malignancies Aloe emodin IL-12p70 INF-a Y. M. Huang, 1 S. Adikari ErpA A*0204 IgE epitopes adenosine G1011A left complement inhibitor factor H. type-4 polysaccharide B19 genome humans Fca ear skin individuals serum mannose-binding lectin A-chain hyperbaric MT2 cells parenteral salmeterol OprI Serum S. aureus serotypes SS IgE. MBL cancer cell fat peptide/MHC noncytopathic lymphocytic choriomeningitis mouse macrophage galactose-type C-type lectin cardiovascular udder Sera O111:B4 cancer patients streptococcal pyrogenic exotoxin C L. OXA leptin receptor NK-cell urea eicosanoid murine monocytic cell lines IL-13 Fel d 1 Lipopolysaccharide arginase1 salivary glands ICOSL Interferon-a/b Lactobacilli lethally transforming growth factor interleukin-4 MBLassociated serine proteases serum samples TIGR4 E. coli IgA2 antibody A2a adenosine receptor TLR2 survivin-specific T cells NK cells human intestine FILEMAKER LXRs sows bax Rix, 1,2 J. Krog L-ficolin/ml IFNg T cells MyD88 peripheral CD4 þ T cells surface skin HLA supertypes peripheral blood neutrophile cell APCs tumour salivary adenocarcinoma breast Human parvovirus B19 nitric oxide aE integrin antigen-loss human monocytes metastatic lesions upper airways Fine Probe volunteers IL-18Ra DC-surface Escherichia coli sera sinFabs oral cancer cells HSP70 Heat shock proteins periparturient IL-4 mononuclear phagocytes rats antigen allergic asthma CD83 lipoprotein I SARS-specific cytotoxic T cell epitopes MNCs granulomas human MnSOD vascular B19 epithelium CD3-CD56bright intravenous Mtb H37Rv man C2 microvascular Dendritic cells query-bycommittee MT2 Fca receptor coelomic saline k562 cells Lactobacillus casei nuclear receptor heterodimers Der p 1 Lactobacillus plantarum gut Lactobacillus rhamnosus GG DAB E. coli lipopolysaccharide alveolar epithelial cell line low-HAZ Vascular peritoneal macrophages children Survivin-derived peptides peripheral blood CD4 þ T cells RANTES piglet vascular lesions high-QBC-enriched 11A, 11D Lactobacillus CD123 CaCo-2 cells B7.2 cellular immune system phagocytes cysteine protease Der p1 CagA IgG antibodies LXR-a blood C3 carcinoma cells Taenia crassiceps M2 Cellular Bacteria-specific IgA antibodies IFN-g blood mononuclear cells IgG CagA vascular endothelial growth factor inhibitory receptor 1 WT control animals Waldenstrom macroglobulinaemia TLR4 k562 encephalitogenic peptide MOG 91-108 IgA. IgG CagA antibodies wound macrophages intracellular IFN-g rat serum albumin cat allergen Fel d 1 2 A. Sanna 1,3 & G. Alm 4 DC antigens ( Mala s 11 KB-cell Borrelia garinii strains epitheloid cells alveolar macrophages airway anticancer lethal tumour cell lines NK-Cell OprI-Ag85A MT Renal A816G SLE. Iga1 nucleus SFC/ Th1-type cytokines NK cell people T-cell lymphoma tumours immunoglobulin ficolins lymphoid SFC rMBL Class I molecules HLA-A1, A2, A3, A11 estrogen receptor-b-Cx Nyboe 10mg/ml UV-inactivated HLA-matched tumour cells Lactobacillus-specific antibodies DCs arginase 1 H. pylori interleukin-4 receptor colonic biopsies myeloid H. pylori IgG nude mice Mice immune cells proliferating cells human MHC project human IL-18 monocyte-derived DCs Monocytes ficolin S. aureus strain MBL/MASP-2 Intramuscular psoriatic lesions macrophage galactose-type C-type lectins blood samples phagosomal HBsAg epidermis pathogen- C4 def. lipid Monocytederived dendritic cells IL-6 collagen-induced arthritis Bronchial Mucosa T lymphocytes TLR adaptor molecules TRIF CD89 Intracellular IFN-g CLA kidney À3 Ab1 human HLA supertypes pSS patients infiltrating macrophages MBL-associated serine proteases human blood monocytes Ag85A CD11b þ HbsAg membrane leukotriene B4 intestinal IgM oral mucosa isoleucine A2a interleukin-13 10mg/ml phytohemagglutinin P21 IAPs Erk1/2 MnSOD S. pneumoniae serotypes LPS persons human blood leucocytes DNA BCG sVEGFR1 CD123 þ EAE IgA2 monoclonal antibodies IL-12 inflammatory cells HBV paramyxovirus Th3 M6 oedema human Sendai virus anti-BrdU antibody mouse Helicobacter pylori B. burgdorferi T helper pigs NAb 5-10 g blood leucocytes TNFa chloride C6 cells human collectins A52R JNK/SAPK macrophage CagA(þ) strains lymph node coronavirus GCs macrophage mannose receptor tissue Flanders platelet cell IgA2 lactobacilli OprI-based prime-boost vaccinations Keratins 16 human lung carcinoma cell line A549 KOs single-chain Fv antibody library macrovascular type 1 IFN RNase L. weaners Sweden. i.v intracellular anthraquinone Vaccinia surface MHC class II Trypanosoma brucei anti-Ro/SSA capsid piglets C1q type-4 polysaccharide-induced interleukin-12 gut mucosa lymphocyte TcHSP70 MHC I CTLs Toll-like receptor 2/4 BDCA2 epithelial cell layer gut flora DA rats malarial antigen EB200 myeloid cells Lactobacillus-specific Ab1 IFNb lymph nodes LLNs inhaled corticosteroid basal cell layer C3 def mouse factor H Seretide 1 psoriatic skin abdominal Th-1 antibody myelin basic protein Pf70C throat C4 def Platelets Th2 effector cells MBL-C suggets Cells CRP BDCA Interleukin-18 human keratin TLRs human phagocytic cell line SARS survivors B cells C4 CD11c granuloma costimulator HLA-B*5801 Th1 GC CD4 SIT WT gastrointestinal lung Romero-Steiner HLA-Cw*0602 basophile histamine HCs MT1 T cells central nervous system Hepatitis B surface antigen Type 1 Diabetes bone marrow-derived murine sugar Pangidis 2 1 inhaled keratin self-antigens oral vascular endothelial growth factor type 2 cytokines gastrointestinal mucosa CD69 tumour necrosis factor (TNF)-a aluminium hydroxide lactic acid high-QBCenriched GC þ patients ICs Treg cell Toll-like receptors DNA cells Ab2 Biotechnology BDCA4 pulmonary Th-1 murine alum A549 cell line Lectin ANA ErpP Vitamins E blood donors pSS Ail high-QBC infiltrate psoriatic skin lesions oral carcinoma Plasma sVEGF C3a OspE. C3-activating enzyme complexes SpeC CD3 BALB/c mice BDCA-1 Bifidobacterium adolescentis Ni2 bowel S. neumoniae IL-2 epithelial tissues MASP complement factor C4 Sjögren's syndrome immune network low-QBC-enriched networks patients lectin MGL B. adolescentis oral epithelia splenic barrier SCRs 3-5 MxA antigen-presenting dendritic cells human dendritic cells virus-specific CD8 þ T cells leaves IgA1 type-4 pneumococci Stockholm, Sweden amino acid BFA IL-8 C3 def. manganese superoxide dismutase IFN-b-induced MxA plasma samples gastric juice HbsAg-MBL HLArestricted IFN Blood cellular B-cell human vaccinees interferon-induced potassium OspE monocyte-derived macrophages splenic CD11b NK-cell-cytotoxic MHC II Adenosine mMGL1 mannan-binding lectin GTPbinding 1⁄4 SP-A herpesvirus [herpes simplex virus Borrelia spirochetes MT1 cells Stockholm ( TNF HSV serum MBL LXR-b arginase CBP-Fel d 1 vitamin E. NK-cell DNA SARS CoV virus-specific CTL Hyperbaric MSCs self-cells H-ficolin/ anticytokine metastatic cancer solid Mal Allergen-specific SLE bronchial Type-1 immune responses against heterologous antigens allergen-coupled CBPs platelets HLA supertype casu peptide-HLA donors T-cell neutrophils human blood donors A2a receptor S. pneumoniae colorectal cancer Patients plasma sVEGF human epidermal keratins human peripheral blood mononuclear cells lung mucosa IL-18 pneumococci valine ( Blood samples bronchial biopsies HLA-B*1501 51Cr human Lactobacillus human monoclonal antibody like ( patient sVEGF neuroectodermal neural networks zone macrophages IFN-a/b TLR plasmacytoid CD11b dendritic cells K17 CD1a androgen receptor IgA A. Astrinidou-Vakaloudi GC-like lesions buffy coats SCRs 18-20 sodium cartilage surface Piglets plasma Human renal MT1 human monoclonal antibody CBPs LDH tumour necrosis factor-a C lysines NK-sensitive IgM DJ NK Blood Cells GM-CSF IL-10 murine monoclonal IgM anti-dsDNA antibody peptide-HLA macrophage antitumour SARS-derived peptide epitopes lung lymph nodes Aerococcus viridans Th2 LABA Mtb IgM-IC À1, 2 costimulator ligand LEW.1AV1 cyclooxygenase-1 MASP-1 human IgA1 tissues Ym ESRD patients CD80 mice IFN-gpositive cells loss-variant tumour cells K16 Bifidobacterium CD8 hapten-exposed sites human factor H joints CD86 monocytes virus nonstructural T-cell surface CD45RA H-ficolin glycoprotein antigens auricular lymph nodes nerve fibre myelin sheets Human Peripheral Blood Mononuclear Cells serum splenic CD11b þ MZM sinFab-molecules endothelial cells IL-12p40 AE germinal centers invertase venous blood Saccharamyces cerevisiae 1⁄4 22 IL-18Rb MASP-2 Faba NKcell PBMC MZM antigenpresenting cells cell double-(his)6-tag L-ficolin Vitamin E GC þ MSC B35 CRC IFN-a bcl-2 polar IgG human gut-derived Lactobacillus submandibular MASP-3 prostate infiltrate dermis littermate type 1 IFNs allergen-specific immune mitochondrial MBL-A (IgV)-like Cw6 Der p1 Cit-RSA T-cell BrdU streptococcus pyogenes L. plantarum Toll-like reseptor 2 oral carcinoma line Streptococcus pneumonia cyanogen-bromide lungs tumour cell HSPs CD103 bronchial asthma macrophage culture cell 1⁄4 5.8696 CD3-CD56dim Plasmodium falciparum MASP-1/3 nonlymphoid cells rat T-cell immunoglobulin-and mucindomain-containing molecule type II cytokine-dependent UV-inactivated gram-positive mucosa Macrophages collagen type II mammalian cells ICS vitamins IgE gastric mucosa tumour cells ABC-kit splenic arginase-producing myeloid suppressor cells proliferating cells 4 HLAwide C. A RA patients nucleoside adenosine XIIIa humeral heterohybridoma MDDCs murine IFN-g blood cells TIM-3 IL-12Rb2 tumours citrulline Ag85A DNA ENA vitamin C organs liver L. reuteri peripheral blood mononuclear cells breast cancer cell line colorectal carcinomas mononuclear cells TCR tumour antigens colorectal cancer CRC specimens oral carcinoma cell line mammary gland IL-18 serine protease 1/2 colon mucosa T-cell clonotypes EpH-4 cells lymph nodes colorectal carcinoma breast cancer donor T cells sentinel nodes cell lines graft-versus-host disease Vb lymphocytes MBL/ MASP bladder cancer Colon samples Cells CRP MBL/MASP cancer urinary bladder cancer LDH peritumoural BCL-6-transduced EpH-4 cells colon breast carcinoma anticancer CD4 human colon mucosa tumour extract mucosa samples Probes epithelial cells EpH-4 cell line Caco-2 IL-1 clonotypes lactate dehydrogenase T-cell receptor KB peripheral blood stem cell grafts CD8 TCR Vb G1/S choriocarcinoma cell line DNA graft-versus-tumour cells serum CRC patients MBL cancer cell MASP-2 Jar cell surfactantprotein-D CRC MASP Peripheral blood samples nonsentinel lymph nodes Gene-chips patients BCL-6 SP-D BMT leukaemia GVHD cancer cells T cells cancer cell lines B-cell mammary epithelium mammary epithelial surfactant protein-A tumour human FACS mucosa colon cancer cell line MASP 1/2 serine proteases mannan-binding mannan-binding lectin SP-A human collectins MCF-7 [ 3 H]-thymidine node lymph node tissue control-transduced EpH-4 cells tumours MNCs blue dye
Extracted Text Content in Record: First 5000 Characters:The nuclear receptor heterodimers of liver X receptors (LXRs) are recently identified as key transcriptional regulators of genes involved in lipid homeostasis and inflammation. LXRs and their ligands are negative regulators of macrophage inflammatory gene expression. Multiple sclerosis (MS), a demyelinating disease of the central nervous system of unknown cause, is characterized by recurrent inflammation involving macrophages and their inflammatory mediators. Sweden belongs to the countries with a high MS incidence. In Italy, incidence is lower, with an exception for Sardinia where the incidence is even higher than that in Sweden. Subjects from Sardinia are ethnically more homogeneous and differ from Swedes, also regarding genetic background and environment. We studied LXRs and their related molecules of blood mononuclear cells (MNCs) from female patients with untreated relapsing-remitting MS from Sassari, Sardinia and Stockholm, Sweden. Sex-and age-matched healthy controls (HCs) were from both areas. mRNA expression was evaluated by real-time PCR. LXR-a was lower (P < 0.05) in MS (mean AE SEM: 3.1 AE 0.2; n 1⁄4 37) compared to HC (3.6 AE 0.1; n 1⁄4 37). LXR-a was lower in MS from Stockholm (2.6 AE 0.2; n 1⁄4 22) compared to corresponding HC (3.4 AE 0.1; n 1⁄4 22; P < 0.01) and compared to MS (3.8 AE 0.2; n 1⁄4 15; P < 0.001) and HC (4 AE 0.2; n 1⁄4 15; P < 0.001) from Sardinia. MS patients from Stockholm, but not from Sassari, also expressed lower (P < 0.05) LXR-b (À4.1 AE 0.4) compared to corresponding HC (À2.9 AE 0.3). MS from Stockholm was associated with higher ABCA-1 (6.1 AE 0.4 versus 5.0 AE 0.3; P < 0.05) and higher estrogen receptor-b-Cx (2.4 AE 0.4 versus 0.8 AE 0.4; P < 0.01) compared to corresponding HC. The HC from Sassari had higher androgen receptor (2.9 AE 0.2) compared to MS from Sassari (1.4 AE 0.3; P < 0.01), MS (1.3 AE 0.4; P < 0.01) and HC from Stockholm (1.2 AE 0.3; P < 0.01). MS from Sassari had lower cyclooxygenase-1 compared to corresponding HC (5.1 AE 0.4 versus 6.6 AE 0.3; P < 0.01) and lower prostaglandin-E (À0.03 AE 0.5) compared to the HC (1.4 AE 0.5; P < 0.05) and MS (2.7 AE 0.4; P < 0.05) and HC from Stockholm (1.9 AE 0.4, P < 0.001). Our findings identify LXRs and their related molecules as being involved in MS from Stockholm but not from Sassari, while sex hormone receptors seem to be involved in MS in Sassari. Multiple Sclerosis: IFN-b Induces CD123 + BDCA2 -Dendritic Cells that Produce IL-6 and IL-10 and have No Enhanced Type I Interferon Production Y. M. Huang, 1 S. Adikari, 1 U. Båve, 2 A. Sanna 1,3 & G. Alm 4 DC antigens (BDCA) and investigate their ability to produce Type I IFN in response to virus stimulation. We show that IFN-b induces development of CD123 þ DC from human blood monocytes, which coexpress BDCA4 þ but are negative for BDCA2 -, a specific marker for plasmacytoid DC. Such IFN-b-modulated DC produce large amounts of IL-6 and IL-10, but no IL-12p40 and have no enhanced IFN-b and IFN-b production. The findings indicate that IFN-bmodulated DC represent a myeloid DC subset with diminished CD11c, BDCA-1 and CD1a expression, having potent Th2-promoting function but lacking antiviral capacity. The association of psoriasis with throat infections by streptococcus pyogenes suggests a potential antigenic target for the T cells that are known to infiltrate dermis and epidermis of psoriatic skin. Streptococcal M protein shares an extensive sequence homology with human epidermal keratins. Keratins 16 (K16) and 17 (K17) are mostly absent from uninvolved skin but are upregulated in psoriatic lesions. There is increasing evidence that CD8 þ T cells play an important effector role in psoriasis and M proteinprimed T cells may recognize these shared epitopes in skin via molecular mimicry. To identify candidate epitopes, peptides with sequences from K17 were selected on the basis of predicted binding to HLA-Cw6 and sequence similarities with M6 protein. Matched peptides from the sequence of M6 protein and a set of peptides with poor predicted binding were also selected. Cw6 þ individuals with psoriasis and Cw6 þ healthy controls, having a family history of psoriasis, were recruited. PBMCs were incubated with the peptide antigens. T-cell activation in the CD4 þ , CD8 þ and later the skin-homing cutaneous lymphocyteassociated antigen (CLA)-expressing subset of CD8 þ T cells was evaluated by CD69 expression and intracellular IFN-g accumulation using flow cytometry. We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. These responses were about 10 times more frequent in the skin-homing cutaneous lymphocyte-associated antigen-expressing (CLA þ ) subset of CD8 þ T cells. CD4 þ T cells showed only borderline responses. CD8 þ T cells from Cw6 þ nonpsoriatic individuals responded to some M6 peptides but very rarely to K17 peptides, and
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