functional and molecular characterization of myeloid suppressor cells expanded during CORD-Papers (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: 2008-06-28
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: 5-10 g Type-1 immune responses against heterologous antigens sinFabs oedema Stockholm ( IgM inhaled gut aluminium hydroxide lectin SCRs 18-20 CD45RA casu peptide-HLA 2 A. Sanna 1,3 & G. Alm 4 DC antigens ( Type 1 Diabetes streptococcal pyrogenic exotoxin C NKcell Vascular DAB TIGR4 Keratins 16 tumour interleukin-4 receptor Th1-type cytokines intercellular contact ErpP 1⁄4 22 keratin self-antigens tissues monocyte-derived dendritic cells CD11b Lipopolysaccharide Class I molecules HLA-A1, A2, A3, A11 NAb monocyte-derived DCs GTPbinding immune network infiltrating macrophages human factor H CD1a Mice MxA human Lactobacillus tissue blood C1q androgen receptor LXRs IgG A-chain granuloma human peripheral blood CD4 þ T cells 10mg/ml phytohemagglutinin donors B7.2 MHC II DA rats HLA-Cw6 sodium S. pneumoniae noncytopathic lymphocytic choriomeningitis A549 cell line CD11c Lactobacillus plantarum platelet cell CD4 IL-13 cyanogen-bromide bcl-2 TNFa abdominal 11A, 11D MBL-C vitamin E type-4 polysaccharide-induced RA patients Iga1 macrophage mannose receptor SCRs 18-20 of factor H intracellular IFN-g IgA2 vascular endothelial growth factor alveolar epithelial cell line 4-colour lymphocytes cat allergen Fel d 1 Plasmodium falciparum HSP70 Survivin-derived peptides platelets CD3-CD56bright mouse factor H humeral sows CagA(þ) strains Seretide 1 AM breast T-cell lymphoma tumours Rix, 1,2 J. Krog HSV liver DNA IL-6 ASMase carcinoma cells MBL-associated serine proteases B-cell type-4 pneumococci SpeC IL-12Rb2 Pangidis 2 1 antigen-presenting dendritic cells MDDCs auricular lymph nodes complement inhibitor factor H. HLA-Cw*0602 APCs IL-8 epitheloid cells cardiovascular citrullin MBP Monocytederived dendritic cells HLA supertypes IgA Th1 lipid saline human gut flora-derived lactobacilli persons plasma anthraquinone CD25 MASP BDCA basal cell layer infiltrate dermis murine IFN-g Nyboe oral carcinoma line mitochondrial OXA epithelial tissues lymph node Macrophage Galactose-Type C-Type Lectins 1 peritoneal macrophages high-QBC Cw6 human peripheral blood mononuclear cells Treg cell Y. M. Huang, 1 S. Adikari macrovascular cancer GC-like lesions Plasma sVEGF monocyte-derived macrophages splenic arginase-producing myeloid suppressor cells epithelium leukotriene B4 oral MT1 weaners salmeterol costimulator NO costimulator ligand IAPs anticancer lung mucosa IgM-IC C3 def. skin O111:B4 allergen-specific immune isoleucine human blood monocytes Platelets splenic CD11b þ MZM Saccharamyces cerevisiae mononuclear phagocytes OspE DNA Lactobacillus casei myelin basic protein IgA antibodies cellular bowel MASP-3 porcine cells Adenosine mMGL2 cells IgG CagA oral mucosa rat serum albumin Fca Toll-like reseptor 2 serum samples Oligochaeta oral epithelia carbohydrate structures salivary adenocarcinoma mast cell nerve fibre myelin sheets IgA1 lymphoid CD123 þ K16 (IgV)-like Borrelia garinii strains BDCA2 C3a C. A T-cell surface Hepatitis B surface antigen CCF-induced macrophage Th-1 low-QBC NK-cell NK-sensitive CagA IgG antibodies B7.1 Th-cell C3 def complement factor C4 S. aureus strain IFN-a/b human IgA1 OspE. AE IgA2 monoclonal antibodies non-NK lineage-specific antibodies mouse macrophage galactose-type C-type lectin Vitamin C macrophage low-QBC-enriched networks MASP-2 B35 arginase 1 IgM DJ Mtb HDM extracts interleukin-13 volunteers Vitamin E YadA B19 genome Th2 effector cells Toll-like receptors TGF-b allergic asthma macrophage galactose-type C-type lectins CaCo-2 CD69 pneumococci serum mannose-binding lectin CD103 1⁄4 Lactobacillus-specific antibodies Sera T-cell cultures human HLA supertypes GC protein-A mannan-binding lectin human epidermal keratins BDCA4 NK-cell-cytotoxic LEW.1AV1 human IL-18 G1011A CTLs Ab2 antibodies blood donors Plasmodium falciparum L. reuteri Ni2 valine ( cancers Pf70C S. pneumoniae serotypes colorectal cancer adenosine sVEGF UV-inactivated gram-positive human lung carcinoma cell line A549 Der p 1 GC þ patients serum MBL FIZZ1 ANA human phagocytic cell line buffy coats Ym IL-2 epidermis CD8 T-cell LABA interleukin-12 antigenpresenting cells bronchial Th-1 antibody neuroectodermal nonlymphoid cells IL-12 monocytes KB-cell C3-activating enzyme complexes humans vitamin C peripheral CD4 þ T cells CD11b þ HBsAg metastatic lesions HLAwide bronchial asthma ENA vitamins Type I Interferon KB-cell line Romero-Steiner human gut-derived Lactobacillus submandibular CBP-Fel d 1 MBLassociated serine proteases gut mucosa DC-surface ICOS pSS Pneumococci Interleukin-18 Th2 Heat shock proteins murine monocytic cell lines TLR sVEGFR1 MHC I human monocytes mice macrophage antitumour Fine ESRD patients anti-Lactobacillus antibodies GM-CSF query-bycommittee cysteine protease Der p1 gastric juice C4 def. plasma sVEGF ficolins airway MT2 ear skin Intramuscular Lactobacillus-specific Ab1 costimulatory IgE epitopes human NK cells LLNs Der p1 HbsAg-specific IgM HCs bacteria-derived antigens SP-A CD83 XIIIa tumour cell lines human MHC project CBPs Hyperbaric Veillonella parvula IL-10 vascular ABC-kit tumour cells mMGL1 ICOSL single-chain Fv antibody library polar lungs wound GC þ B cells basophile histamine BFA Ab1 SARS-derived peptide epitopes CLA endothelial cells BALB/c mice cancer cell mucosa FHR-1 colonic biopsies SLE. L. H. pylori IgG type II cytokine-dependent allergen-coupled CBPs salivary gland tissue macrophages Lactobacillus spleen peripheral blood IFN-g TIM-3 virus-specific CTL TLR2 antigen-loss Blood samples C5a anaphylatoxins Mal thymidine À1, 2 splenic CD11b alum IL-18 human monoclonal antibody like ( PD-L2 51Cr Bifidobacterium individuals MSCs Allergen-specific MSC zone macrophages vascular endothelial growth factor inhibitory receptor 1 CaCo-2 cells myeloid cells Blood Bronchial Mucosa T lymphocytes NK-cell DNA double-(his)6-tag gastric mucosa renal intestinal SFC MT2/MT1 anticytokine IFN nude mice cell mammalian cell pathogen- C4 TLR adaptor molecules TRIF MGL Fel d 1 SARS-specific cytotoxic T cell epitopes B19 tumours Interferon-a/b i.v Taenia crassiceps DCs IL-18Rb Sweden. SCRs 3-5 SS lactic acid Sendai virus HLA-matched tumour cells MNCs human intestine neural networks murine RNase L. periparturient HDM A816G MT2 cells nucleus INF-a infiltrate psoriatic skin lesions MT1 T cells IL-18Ra BCG IAP TLRs chloride oral carcinoma lymphocyte capsid myeloid H. pylori hyperbaric epithelial layers NK bronchial biopsies lethal 1⁄4 5.8696 WT human blood leucocytes L-ficolin CD89 C6 cells immune cells HLA supertype human dendritic cells B. burgdorferi Escherichia coli interferon-induced throat IAPderived CD123 human collectins Blood Cells OprI-based prime-boost vaccinations alveolar macrophages A52R blood leucocytes Cellular IL-5 IgA2 antibody high-QBC-enriched fat S. neumoniae human MnSOD MBL dendritic cells malignancies NK cell E. coli lipopolysaccharide human vaccinees peptide-HLA k562 cells MyD88 Human WT control animals kidney V. parvula cyclooxygenase-1 paramyxovirus IFNg virus nonstructural liver X receptors serum rMBL IL-12p40 Patients Ail Sjögren's syndrome Vaccinia Vitamins E A*0204 Erk1/2 sugar Annelida GCs granulomas HLA-B*1501 malarial antigen EB200 Th3 proliferating cells NK cells vascular endothelium vitamin E. lung arginase1 collagen type II IL-4 metastatic cancer À3 Trypanosoma cruzi plasma samples Flanders anti-Ro/SSA IgE. manganese superoxide dismutase surface lactobacilli CD80 peptide/MHC Intracellular IFN-g i.n oral cancer cells ICS ceramide Lactobacilli SARS CoV Renal H. sera aE integrin blood cells fibrin CD86 LDH FILEMAKER plasmacytoid PBMC BrdU TNF immunoglobulin TNF-a arginase phagosomal bax neutrophile cell vascular lesions 10mg/ml UV-inactivated suggets coelomic sinFab-molecules high-QBCenriched cancer patients type-4 polysaccharide inhaled corticosteroid C2 IFNb Ag85A DNA M6 organs leaves IgA1 Dendritic cells piglet SFC/ Bacteria-specific IgA antibodies tumour cell urea Fca receptor pigs IFN-a Cells MnSOD estrogen receptor-b-Cx A. Astrinidou-Vakaloudi IFN-gpositive cells EAE Cell streptococcus pyogenes lipoprotein I Ag85A LPS hepatocellular carcinoma microvascular littermate A2a receptor A2a citrulline Human Peripheral Blood Mononuclear Cells IgE parenteral salivary glands Mala s 11 SARS survivors tumour necrosis factor (TNF)-a lung lymph nodes children rat T-cell immunoglobulin-and mucindomain-containing molecule SIT pulmonary LXR-a BDCA-1 blood samples HLA-B*5801 C prostate Stockholm, Sweden LXR-b collagen-induced arthritis rats HBV coronavirus MASP-1/3 18:213-25 type 2 cytokines upper airways KOs k562 Macrophages HLArestricted L. plantarum M2 gastrointestinal Human parvovirus B19 loss-variant tumour cells interleukin-4 patient Faba hyperimmunized mice OprI SLE B-chains ficolin mammalian cells blood mononuclear cells MBL-A heterohybridoma Biotechnology herpesvirus [herpes simplex virus membrane nucleoside adenosine people TLR4 Aloe emodin Probe Serum A2a adenosine receptor Borrelia spirochetes joints E. coli fluticasone propionate MZM HSPs PBMCs Heat Shock Protein 70 antigen leptin receptor invertase phagocytes left cellular immune system solid C4 def Aerococcus viridans psoriatic skin S. aureus serotypes marginal zone macrophages nuclear receptor heterodimers human monoclonal antibody NK-Cell cartilage surface patients self-cells ICs CRC human keratin Toll-like receptor 2/4 potassium epithelial cell layer encephalitogenic peptide MOG 91-108 peripheral blood mononuclear cells type I allergen mouse amino acid central nervous system proliferating cells 4 nitric oxide K17 TcHSP70 macrophage culture cell glycoprotein antigens low-HAZ Natural Killer Cell OprI-Ag85A JNK/SAPK lymph nodes gut flora Ab2 Lactobacillus rhamnosus GG type 1 IFN piglets bone marrow-derived murine CD3-CD56dim hl60 Bifidobacterium adolescentis splenic barrier ErpA type 1 IFNs virus-specific CD8 þ T cells venous blood survivin-specific T cells psoriatic lesions IFN-b-induced MxA inflammatory cells MBL/MASP-2 lethally C3 MT1 cells germinal centers RANTES murine monoclonal IgM anti-dsDNA antibody eicosanoid transforming growth factor lysines P21 B. adolescentis Helicobacter pylori intracellular IgA. IgG CagA antibodies T cells man pSS patients HSP70 HbsAg-MBL tumour necrosis factor-a Streptococcus pneumonia human blood donors HbsAg CRP H-ficolin/ Waldenstrom macroglobulinaemia IL-12p70 Trypanosoma brucei neutrophils CD3 Cit-RSA T-cell Monocytes interleukin 2 hapten-exposed sites Type I IFN udder Lectin anti-BrdU antibody intravenous Mtb H37Rv T helper Piglets surface MHC class II gastrointestinal mucosa MT MASP-1 L-ficolin/ml H-ficolin graft-versus-tumour graft-versus-host disease colon cancer cell line IL-18 MBL/ MASP tumour Cells mononuclear cells CRC specimens peritumoural tumour antigens Probes serine proteases mannan-binding MASP-2 tissue TCR Vb colorectal carcinoma node human cell sentinel nodes control-transduced EpH-4 cells choriocarcinoma cell line surfactant protein-A tumours FACS CD4 mannan-binding lectin mammary epithelium MCF-7 BCL-6-transduced EpH-4 cells Peripheral blood samples breast carcinoma colon mucosa mucosa samples MNCs colorectal cancer urinary bladder cancer TCR breast cancer cell line bladder cancer lymphocytes CD8 G1/S Gene-chips [ 3 H]-thymidine mammary gland human collectins human colon mucosa KB B-cell patients CRC MASP 1/2 MBL MBL/MASP nonsentinel lymph nodes cancer cells BMT T-cell clonotypes BCL-6 GVHD lymph nodes SP-D serum IL-1 MASP surfactantprotein-D EpH-4 cell line cancer cell lines Jar Colon samples lymph node colorectal carcinomas T-cell receptor cancer breast cancer serine protease 1/2 oral carcinoma cell line lactate dehydrogenase peripheral blood stem cell grafts blue dye leukaemia T cells SP-A colon anticancer Caco-2 LDH donor T cells CRP mammary epithelial DNA clonotypes epithelial cells CRC patients tumour extract cells cancer cell mucosa cell lines EpH-4 cells Vb
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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