Frontline Science: Tim-3-mediated dysfunctional engulfment of apoptotic cells in SLE.

Abstract:

:T cell Ig and mucin domain-containing molecule 3 (Tim-3) has been found to play important roles in autoimmune diseases, but whether Tim-3-mediated engulfment of apoptotic cells is involved in systemic lupus erythematosus (SLE) remains to be elucidated. In this study, we verified the role of human Tim-3 (hTim-3) as the receptor of phosphatidylserine (PS) in human embryonic kidney (HEK)293 cells, which initiated the engulfment of apoptotic cells. Both IgV and the mucin domain of Tim-3 were crucial in the phagocytosis of apoptotic cells, and there existed the key cytoplasmic domain for signal transduction. Alanine at 111, locating around the FG-CC' loop of hTim-3, was necessary for its engulfment of apoptotic cells. In accordance, Tim-3 on CD14+ cells negatively correlated with the percentage of peripheral apoptotic cells in control subjects. However, although Tim-3 was significantly increased on CD14+ cells in SLE patients, peripheral apoptotic cells remained much higher than those in control subjects. Tim-3 on CD14+ cells showed positive correlation with percentage of apoptotic cells and level of dsDNA, indicating the involvement of Tim-3 in SLE. Accordingly, soluble Tim-3 (sTim-3) was significantly increased in plasma of SLE patients, which might contribute to higher expression of a disintegrin and metalloproteinase (ADAM)-10. Pretreatment with both plasma from SLE patients and recombinant sTim-3 greatly inhibited hTim-3-initiated phagocytosis of apoptotic cells. Furthermore, anti-Tim-3 antibody depletion of plasma from SLE patients reversed the decreased phagocytosis of apoptotic cells. Collectively, our data suggest that sTim-3 might play inhibitory roles in impaired Tim-3-mediated clearance of apoptotic cells in SLE.

journal_name

J Leukoc Biol

authors

Zhao D,Guo M,Liu B,Lin Q,Xie T,Zhang Q,Jia X,Shu Q,Liang X,Gao L,Ma C

doi

10.1189/jlb.3HI0117-005RR

subject

Has Abstract

pub_date

2017-12-01 00:00:00

pages

1313-1322

issue

6

eissn

0741-5400

issn

1938-3673

pii

jlb.3HI0117-005RR

journal_volume

102

pub_type

杂志文章
  • Novel insights into the inhibitory effects of Galectin-1 on neutrophil recruitment under flow.

    abstract::Galectin-1 (Gal-1) is a beta-galactoside-binding protein endowed with anti-inflammatory properties. The purpose of this study was to investigate the effects of endogenous and exogenous Gal-1 on neutrophil recruitment onto TNF-treated endothelium. The effect of human recombinant (hr)Gal-1 on markers of neutrophil activ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.1207831

    authors: Cooper D,Norling LV,Perretti M

    更新日期:2008-06-01 00:00:00

  • Cellular and viral determinants that regulate HIV-1 infection in macrophages.

    abstract::Macrophages in brain, lung, and lymphatics constitute a major HIV reservoir during subclinical infection and disease. During HIV transmission macrophages are seemingly one of the first cells infected, being as efficient as T cells in supporting productive viral replication. Macrophages control a myriad of cell-mediate...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1002/jlb.56.3.278

    authors: Stevenson M,Gendelman HE

    更新日期:1994-09-01 00:00:00

  • The monoclonal antibody MAC387 detects an epitope on the calcium-binding protein MRP14.

    abstract::The present study was initiated to identify the antigen recognized by the monoclonal antibody (MAb) MAC387 which is widely used for phenotypical characterization of myelomonocytic cells in situ. MAC387 has been described to show a similar reaction pattern as antisera to a complex formed by the calcium-binding proteins...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.55.2.259

    authors: Goebeler M,Roth J,Teigelkamp S,Sorg C

    更新日期:1994-02-01 00:00:00

  • The role of calcium in the regulation of apoptosis.

    abstract::The recognition that apoptosis is regulated by an evolutionarily conserved set of polypeptides from the nematode Caenorhabditis elegans to humans suggests that a conserved set of biochemical mechanisms may also he involved in the response. Work from a number of independent laboratories suggests that alterations in cyt...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:

    authors: McConkey DJ,Orrenius S

    更新日期:1996-06-01 00:00:00

  • CpG-B ODNs potently induce low levels of IFN-alphabeta and induce IFN-alphabeta-dependent MHC-I cross-presentation in DCs as effectively as CpG-A and CpG-C ODNs.

    abstract::Deoxycytidyl-deoxyguanosine [(CpG)3] oligodeoxynucleotides (ODNs) signal through TLR9 to induce type-I IFN (IFN-alphabeta) and IFN-alphabeta-dependent MHC-I cross-presentation of exogenous antigens by dendritic cells (DCs). A puzzle was presented by our observation that three ODN classes, CpG-A, CpG-B, and CpG-C, had ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.1006606

    authors: Gray RC,Kuchtey J,Harding CV

    更新日期:2007-04-01 00:00:00

  • Detection of the production of oxygen-centered free radicals by human neutrophils using spin trapping techniques: a critical perspective.

    abstract::Human neutrophils generate oxygen reduction products as a consequence of membrane interactions with a number of stimuli. One oxygen-centered free radical (superoxide) has been unequivocally shown to result from this "respiratory burst," and some experimental evidence for another (hydroxyl radical) has been published, ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:10.1002/jlb.41.4.349

    authors: Britigan BE,Cohen MS,Rosen GM

    更新日期:1987-04-01 00:00:00

  • Alcohol-induced IL-1β in the brain is mediated by NLRP3/ASC inflammasome activation that amplifies neuroinflammation.

    abstract::Alcohol-induced neuroinflammation is mediated by proinflammatory cytokines, including IL-1β. IL-1β production requires caspase-1 activation by inflammasomes-multiprotein complexes that are assembled in response to danger signals. We hypothesized that alcohol-induced inflammasome activation contributes to increased IL-...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.1212659

    authors: Lippai D,Bala S,Petrasek J,Csak T,Levin I,Kurt-Jones EA,Szabo G

    更新日期:2013-07-01 00:00:00

  • Unmethylated CpG motifs in the L. donovani DNA regulate TLR9-dependent delay of programmed cell death in macrophages.

    abstract::Regulation of macrophage PCD plays an important role in pathogenesis of leishmaniasis. However, the precise involvement of any parasite molecule in this process remains uncertain. In the current study, in silico wide analysis demonstrated that genes in the Leishmania donovani genome are highly enriched for CpG motifs,...

    journal_title:Journal of leukocyte biology

    pub_type: 临床试验,杂志文章

    doi:10.1189/jlb.4A0713-378RR

    authors: Das S,Ghosh AK,Singh S,Saha B,Ganguly A,Das P

    更新日期:2015-02-01 00:00:00

  • Cross-talk between toll-like receptors 5 and 9 on activation of human immune responses.

    abstract::The recognition of pathogen-associated molecular patterns by TLRs triggers the activation of innate and adaptive immune responses. Flagellin, the agonist of TLR5, is expressed by prokaryotes and eukaryotes, and DNA sequences containing unmethylated CpG dinucleotides, agonists of TLR9, are present essentially in prokar...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0207100

    authors: Merlo A,Calcaterra C,Mènard S,Balsari A

    更新日期:2007-09-01 00:00:00

  • Selective expansion of perforin-positive CD8+ T cells by immature dendritic cells infected with live Bacillus Calmette-Guérin mycobacteria.

    abstract::Live, but not dead Bacillus Calmette-Guérin (BCG) is partially protective against infection by Mycobacterium tuberculosis, which causes a disease with high mortality in immune compromised individuals. We have shown that uptake of BCG induces maturation of immature dendritic cells (DCs) regardless of the viability of t...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:

    authors: Tsunetsugu-Yokota Y,Tamura H,Tachibana M,Ogata K,Honda M,Takemori T

    更新日期:2002-07-01 00:00:00

  • Angiopoietin-mediated endothelial P-selectin translocation: cell signaling mechanisms.

    abstract::Recently identified, angiopoietin-1 (Ang1) and -2 (Ang2) bind to the tyrosine kinase receptor Tie2 and contribute to orchestrate blood vessel formation during angiogenesis. Ang1 mediates vessel maturation and integrity by favoring the recruitment of pericytes and smooth muscle cells. Ang2, initially identified as a Ti...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0107056

    authors: Maliba R,Brkovic A,Neagoe PE,Villeneuve LR,Sirois MG

    更新日期:2008-02-01 00:00:00

  • Frontline Science: Corticotropin-releasing factor receptor subtype 1 is a critical modulator of mast cell degranulation and stress-induced pathophysiology.

    abstract::Life stress is a major risk factor in the onset and exacerbation of mast cell-associated diseases, including allergy/anaphylaxis, asthma, and irritable bowel syndrome. Although it is known that mast cells are highly activated upon stressful events, the mechanisms by which stress modulates mast cell function and diseas...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.2HI0317-088RR

    authors: Ayyadurai S,Gibson AJ,D'Costa S,Overman EL,Sommerville LJ,Poopal AC,Mackey E,Li Y,Moeser AJ

    更新日期:2017-12-01 00:00:00

  • Flagellin preconditioning enhances the efficacy of mesenchymal stem cells in an irradiation-induced proctitis model.

    abstract::The success of mesenchymal stem cell transplantation for proctitis depends not only on cell donors but also on host microenvironmental factors, which play a major role in conditioning mesenchymal stem cell immunosuppressive action and repair. This study sought to determine if flagellin, a TLR5 ligand, can enhance the ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.3A0915-393R

    authors: Linard C,Strup-Perrot C,Lacave-Lapalun JV,Benderitter M

    更新日期:2016-09-01 00:00:00

  • Induction of cyclooxygenase-2 expression during HIV-1-infected monocyte-derived macrophage and human brain microvascular endothelial cell interactions.

    abstract::Human immunodeficiency virus type-1 (HIV-1)-associated dementia (HAD) is a neurodegenerative disease characterized by HIV infection and replication in brain tissue. HIV-1-infected monocytes overexpress inflammatory molecules that facilitate their entry into the brain. Prostanoids are lipid mediators of inflammation th...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:

    authors: Pereira CF,Boven LA,Middel J,Verhoef J,Nottet HS

    更新日期:2000-09-01 00:00:00

  • Selenium and the immune response: 1. Modulation of alloreactive human lymphocyte functions in vitro.

    abstract::A role for the dietary trace mineral element selenium in the reduction of cancer incidence has been documented in numerous epidemiological and experimental studies. The precise mechanism of this antitumor effect is not well understood, but published data suggest that both inhibition of tumor cell growth and enhancemen...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.45.3.207

    authors: Petrie HT,Klassen LW,Kay HD

    更新日期:1989-03-01 00:00:00

  • The mucosal immune system: from control of inflammation to protection against infections.

    abstract::The IV meeting of the European Mucosal Immunology Group, held October 8-10, 2004, in Lyon, gathered fundamental and clinical research scientists to discuss the most recent updates on basic and clinical aspects of mucosal immunology. The meeting was focused on innate and acquired immune mechanisms underlying handling a...

    journal_title:Journal of leukocyte biology

    pub_type:

    doi:10.1189/jlb.0105053

    authors: Kaiserlian D,Cerf-Bensussan N,Hosmalin A

    更新日期:2005-08-01 00:00:00

  • Migration of monocytes after intracerebral injection at entorhinal cortex lesion site.

    abstract::The lack of classical lymph vessels within brain tissue complicates immune surveillance of the CNS, and therefore, cellular emigration out of the CNS parenchyma requires alternate pathways. Whereas invasion of blood-derived mononuclear cells and their transformation into ramified, microglia-like cells in areas of axon...

    journal_title:Journal of leukocyte biology

    pub_type: 评论,杂志文章

    doi:10.1189/jlb.0511241

    authors: Kaminski M,Bechmann I,Pohland M,Kiwit J,Nitsch R,Glumm J

    更新日期:2012-07-01 00:00:00

  • Homologous recombination into the eosinophil peroxidase locus generates a strain of mice expressing Cre recombinase exclusively in eosinophils.

    abstract::Eosinophils are generally linked to innate host defense against helminths, as well as the pathologies associated with allergic diseases, such as asthma. Nonetheless, the activities of eosinophils remain poorly understood, which in turn, has prevented detailed definitions of their role(s) in health and disease. Homolog...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0213089

    authors: Doyle AD,Jacobsen EA,Ochkur SI,Willetts L,Shim K,Neely J,Kloeber J,Lesuer WE,Pero RS,Lacy P,Moqbel R,Lee NA,Lee JJ

    更新日期:2013-07-01 00:00:00

  • CTLA4-CD80/CD86 interactions on primary mouse CD4+ T cells integrate signal-strength information to modulate activation with Concanavalin A.

    abstract::The mechanisms by which concanavalin A (Con A), a lectin, activates T cells are poorly studied. A low dose of Con A is stimulatory for T cells, whereas a high dose of Con A results in suppression of proliferation and enhanced T cell death. The expression and functional roles of costimulatory receptors, CD28 and cytoto...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.1104644

    authors: Mukherjee S,Ahmed A,Nandi D

    更新日期:2005-07-01 00:00:00

  • HIV gp41-induced apoptosis is mediated by caspase-3-dependent mitochondrial depolarization, which is inhibited by HIV protease inhibitor nelfinavir.

    abstract::Apoptotic loss of CD4+ T cells has been proposed as a mechanism of T cell depletion in human immunodeficiency virus (HIV) infections resulting in immunodeficiency. The Env glycoprotein has been implicated in apoptosis of uninfected bystander cells via gp120 binding to CD4/CXC chemokine receptor 4 as well as the fusion...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0805430

    authors: Garg H,Blumenthal R

    更新日期:2006-02-01 00:00:00

  • The effect of adenovirus-specific antibodies on adenoviral vector-induced, transgene product-specific T cell responses.

    abstract::In this study, we tested the effect of neutralizing Abs to different serotypes of E1-deleted Ad vectors on the immunogenicity of the homologous Ad vector or a vector derived from a heterologous serotype. Our results showed that, as expected, even low titers of passively transferred neutralizing Abs significantly reduc...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.1A0813-451RR

    authors: Small JC,Haut LH,Bian A,Ertl HC

    更新日期:2014-11-01 00:00:00

  • Prenylation of an interferon-gamma-induced GTP-binding protein: the human guanylate binding protein, huGBP1.

    abstract::Interferons (IFN) and lipopolysaccharide (LPS) cause multiple changes in isoprenoid-modified proteins in murine macrophages, the most dramatic being the expression of a prenyl protein of 65 kDa. The guanylate binding proteins (GBPs) are IFN-inducible GTP-binding proteins of approximately 65 kDa that possess a CaaX mot...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.60.3.423

    authors: Nantais DE,Schwemmle M,Stickney JT,Vestal DJ,Buss JE

    更新日期:1996-09-01 00:00:00

  • The human promyelocytic leukemia cell (HL-60 cell) beta-adrenergic receptor.

    abstract::We have characterized the beta-adrenergic receptor binding site and the beta-adrenergic cAMP response of the HL-60 cell. The hydrophilic ligand [3H]-(-)-CGP-12177 was specifically and reversibly bound to one single class of binding sites (Kd 220 pM and Bmax 1,970 sites/cell). The adrenergic agonists inhibited the spec...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.44.1.41

    authors: Sager G,Bang BE,Pedersen M,Aarbakke J

    更新日期:1988-07-01 00:00:00

  • miR-181c-BRK1 axis plays a key role in actin cytoskeleton-dependent T cell function.

    abstract::MicroRNAs are short endogenous noncoding RNAs that play pivotal roles in a diverse range of cellular processes. The miR-181 family is important in T cell development, proliferation, and activation. In this study, we have identified BRK1 as a potential target of miR-181c using a dual selection functional assay and have...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/JLB.1A0817-325RR

    authors: Lim SP,Ioannou N,Ramsay AG,Darling D,Gäken J,Mufti GJ

    更新日期:2018-05-01 00:00:00

  • Coupling of C3bi to IgG inhibits the tyrosine phosphorylation signaling cascade downstream Syk and reduces cytokine induction in monocytes.

    abstract::The effect of coupling C3bi to immunoglobulin G (IgG) immune complexes (IC) on their ability to produce protein tyrosine phosphorylation and activation of the mitogen-activated protein kinase (MAPK) and the Akt/protein kinase B (PKB) routes was assessed in human monocytes. Cross-linking Fc receptors for IgG activated ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.1205701

    authors: Trinidad AG,de la Puerta ML,Fernández N,Bayón Y,Crespo MS,Alonso A

    更新日期:2006-05-01 00:00:00

  • Inflammation, immunoregulation, and inducible nitric oxide synthase.

    abstract::Nitric oxide (NO), the molecule of the year 1992, is gaining recognition as an important biological mediator. Its multitude of physiologic and pathophysiologic functions result from both a wide distribution of synthesis and diverse mechanisms of action. Besides its functions as a potent vasodilator and neurotransmitte...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审

    doi:

    authors: Nussler AK,Billiar TR

    更新日期:1993-08-01 00:00:00

  • Neutrophil-derived matrix metalloproteinase-9 is a potent activator of trypsinogen in acinar cells in acute pancreatitis.

    abstract::MMPs are generally considered to regulate degradation and remodeling of the ECM. Convincing data also implicate a role for MMPs in inflammatory conditions, such as AP, although the mechanisms are not known. The aim of this study was to define the role of MMPs in regulating activation of trypsinogen and tissue damage i...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0811443

    authors: Awla D,Abdulla A,Syk I,Jeppsson B,Regnér S,Thorlacius H

    更新日期:2012-05-01 00:00:00

  • The significance of carbohydrates on G-CSF: differential sensitivity of G-CSFs to human neutrophil elastase degradation.

    abstract::It has been reported recently that granulocyte-colony stimulating factor (G-CSF) is degraded upon exposure to human neutrophil elastase (HNE), and this has a negative effect on the ability of the cytokine to promote the in vitro proliferation and maturation of CD34+ cells. This has important implications on the possib...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0803378

    authors: Carter CR,Whitmore KM,Thorpe R

    更新日期:2004-03-01 00:00:00

  • Dual function of human IgA antibodies: inhibition of phagocytosis in circulating neutrophils and enhancement of responses in IL-8-stimulated cells.

    abstract::We have sought to elucidate the responses of human peripheral blood neutrophils to antigenic surfaces complexed with human specific IgA antibodies obtained either as myeloma proteins that recognize staphylococcal alpha-toxin, or from the serum of patients with subacute bacterial endocarditis due to Streptococcus mutan...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1002/jlb.57.6.875

    authors: Nikolova EB,Russell MW

    更新日期:1995-06-01 00:00:00

  • HLA-A2 down-regulation on primary human macrophages infected with an M-tropic EGFP-tagged HIV-1 reporter virus.

    abstract::Multiple mechanisms are used by the human immunodeficiency virus type 1 (HIV-1) to interfere with host-cell immune effector functions. The 27-kD Nef protein has been shown to down-modulate specific genes of the major histocompatibility complex class I (MHC-I) on the surface of infected primary T cells, facilitating th...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章

    doi:10.1189/jlb.0505237

    authors: Brown A,Gartner S,Kawano T,Benoit N,Cheng-Mayer C

    更新日期:2005-09-01 00:00:00