Abstract：
:Acute graft-versus-host disease (aGvHD) is still a major cause of transplant-related mortality after allogeneic stem cell transplantation (ASCT). It requires immunosuppressive treatments that broadly abrogate T cell responses including beneficial ones directed against tumor cells or infective pathogens. Polo-like kinase 1 (PLK1) is overexpressed in many cancer types including leukemia, and clinical studies demonstrated that targeting PLK1 using selective PLK1 inhibitors resulted in inhibition of proliferation and induction of apoptosis predominantly in tumor cells, supporting the feasibility of PLK1 as target for anticancer therapy. Here, we show that activation of alloreactive T cells (Tallo) up-regulate expression of PLK1, suggesting that PLK1 is a potential new candidate for dual therapy of aGvHD and leukemia after ASCT. Inhibition of PLK1, using PLK1-specific inhibitor GSK461364A selectively depletes Tallo by preventing activation and by inducing apoptosis in already activated Tallo, while memory T cells are preserved. Activated Tallo cells which survive exposure to PLK1 undergo inhibition of proliferation by induction of G2/M cell cycle arrest, which is accompanied by accumulation of cell cycle regulator proteins p21(WAF/CIP1), p27(Kip1), p53 and cyclin B1, whereas abundance of CDK4 decreased. We also show that suppressive effects of PLK1 inhibition on Tallo were synergistically enhanced by concomitant inhibition of molecular chaperone Hsp90. Taken together, our data suggest that PLK1 inhibition represents a reasonable dual strategy to suppress residual tumor growth and efficiently deplete Tallo, and thus provide a rationale to selectively prevent and treat aGvHD.
journal_name
Immunol Resjournal_title
Immunologic researchauthors
Berges C,Chatterjee M,Topp MS,Einsele Hdoi
10.1007/s12026-015-8778-2subject
Has Abstractpub_date
2016-06-01 00:00:00pages
687-98issue
3eissn
0257-277Xissn
1559-0755pii
10.1007/s12026-015-8778-2journal_volume
64pub_type
杂志文章abstract：:Histones appear in plasma during infectious or non-infectious sepsis and are associated with multiorgan injury. In the current studies, intravenous infusion of histones resulted in their localization in major organs. In vitro exposure of mouse macrophages to histones caused a buildup of histones on cell membranes foll...
journal_title：Immunologic research
pub_type： 杂志文章
doi：10.1007/s12026-015-8628-2
更新日期：2015-03-01 00:00:00
abstract：:CD27 is a tumor necrosis factor (TNF) receptor family member whose expression is limited to cells of the lymphoid lineage. Constitutively expressed on T lymphocytes, it is a costimulatory molecule for a regulatory subset. Induced on B lymphocytes after antigenic challenge, it is a marker of memory cells. CD70, CD27 li...
journal_title：Immunologic research
pub_type： 杂志文章,评审
doi：10.1385/IR:21:1:23
更新日期：2000-01-01 00:00:00
abstract：:Natural killer cells play a major role in innate immunity against tumor and virus-infected cells. NK cells express activating and inhibitory receptors to regulate their function. It has been established that modulation in the NK cell receptor profile results in altered function of NK cell against target cells. Here, w...
journal_title：Immunologic research
pub_type： 杂志文章
doi：10.1007/s12026-017-8982-3
更新日期：2018-02-01 00:00:00
abstract：:The goal of our work is to understand, from the molecular to the organismal level, the principles that drive and sustain lifelong infection by viruses. These infectious agents live in a dynamic equilibrium (homeostasis) with their hosts in which both immune and nonimmune pathways contribute to viral homeostasis. Disru...
journal_title：Immunologic research
pub_type： 杂志文章,评审
doi：10.1385/IR:21:2-3:219
更新日期：2000-01-01 00:00:00
abstract：:Systemic sclerosis (SSc) is an intractable multifaceted disease with high mortality. Although its pathogenesis is not fully understood, recent studies have advanced our knowledge on SSc. The cardinal pathological features of SSc are autoimmunity, vasculopathy, and fibrosis. The B cells in SSc are constitutively activa...
journal_title：Immunologic research
pub_type： 杂志文章,评审
doi：10.1007/s12026-017-8926-y
更新日期：2017-08-01 00:00:00
abstract：:Herpes simplex virus type 1 infection of the mouse eye results in an impressive inflammatory response culminating in the death of the animal or the establishment of a "latent" infection depending on a number of ill-defined variables that include components of the innate and adaptive immune system. The application of t...
journal_title：Immunologic research
pub_type： 杂志文章
doi：10.1385/IR:30:2:191
更新日期：2004-01-01 00:00:00
abstract：:Chronic inflammation mediated by microglial cells is the fundamental process contributing to the death of dopamine (DA)-producing neurons in the brain. Production of inflammatory products by these microglial cells characterizes the slow destructive process in Parkinson's disease (PD). The activation of microglial cell...
journal_title：Immunologic research
pub_type： 杂志文章
doi：10.1007/s12026-008-8018-0
更新日期：2008-01-01 00:00:00
abstract：:Immune cell development and function must be tightly regulated through cell surface receptors to ensure proper responses to pathogen and tolerance to self. In T cells, the signal from the T-cell receptor is essential for T-cell maturation, homeostasis, and activation. In mast cells, the high-affinity receptor for IgE ...
journal_title：Immunologic research
pub_type： 杂志文章
doi：10.1007/s12026-010-8175-9
更新日期：2011-04-01 00:00:00
abstract：:In recent years, there has been a growing interest in the role of immune, alloimmune and autoimmune processes in the pathogenesis of spontaneous preterm birth and recurrent pregnancy loss. The association between an inflammatory response and preterm labor has been established. Indeed, many women suffering from preterm...
journal_title：Immunologic research
pub_type： 杂志文章,评审
doi：10.1007/s12026-014-8621-1
更新日期：2015-02-01 00:00:00
abstract：:In the murine splenocytes, CD8α+ dendritic cells (abbreviated as 8+DC) and CD8α- dendritic cells (abbreviated as 8-DC) are identified with some vague features for each of them. 8+DCs but not 8-DCs cross-prime cytotoxic T cells in vivo. We aim to distinguish the two subtypes of DC based on gene expression profiling. Su...
journal_title：Immunologic research
pub_type： 杂志文章
doi：10.1007/s12026-011-8237-7
更新日期：2011-10-01 00:00:00
abstract：:Recent studies have elucidated unanticipated connections between the immune and skeletal systems, and this relationship has led to the development of a new field known as osteoimmunology. The goal of research in this field is to: (1) further understand how the bone microenvironment influences immune cell ontogeny and ...
journal_title：Immunologic research
pub_type： 杂志文章,评审
doi：10.1007/s12026-009-8093-x
更新日期：2009-12-01 00:00:00
abstract：:Antimicrobial peptide innate immunity plays a central role in the susceptibility to infectious diseases, as has been described extensively in different settings. However, the role that these molecules play in the immunity mediated by polymorphonuclear phagocytes as part of the innate immunity of ageing individuals has...
journal_title：Immunologic research
pub_type： 杂志文章
doi：10.1007/s12026-015-8689-2
更新日期：2016-04-01 00:00:00
abstract：:Bronchiolitis obliterans organizing pneumonia (BOOP) is defined by buds of granulation tissue within lung distal airspaces. The diagnosis requires the histopathologic evidence of organizing pneumonia along with a suggestive clinical and radiographic pattern. This disorder is characterized by a good response to cortico...
journal_title：Immunologic research
pub_type： 杂志文章,评审
doi：10.1007/s12026-014-8607-z
更新日期：2015-02-01 00:00:00
abstract：:Allergic asthma is a chronic disease of the lung characterized by underlying Th2- and IgE-mediated inflammation, structural alterations of the bronchial wall, and airway hyperresponsiveness. Initial allergic sensitization and later development of chronic disease are determined by close interactions between lung struct...
journal_title：Immunologic research
pub_type： 杂志文章,评审
doi：10.1007/s12026-012-8296-4
更新日期：2012-09-01 00:00:00
abstract：:Although the B-cell antigen receptor (BCR) factors most prominently in the maintenance and differentiation of mature B cells, it is now appreciated that co-receptor molecules can positively or negatively modulate signals through the BCR. Co-receptors are functionally defined as modifiers of BCR engagement and signal t...
journal_title：Immunologic research
pub_type： 杂志文章,评审
doi：10.1385/IR:31:2:119
更新日期：2005-01-01 00:00:00
abstract：:Cell-penetrating peptides (CPP) or membrane-translocating peptides such as penetratin from Antennapedia homeodomain or TAT from human immunodeficiency virus are useful vectors for the delivery of protein antigens or their cytotoxic (Tc) or helper (Th) T cell epitopes to antigen-presenting cells. Mice immunized with CP...
journal_title：Immunologic research
pub_type： 杂志文章
doi：10.1007/s12026-016-8799-5
更新日期：2016-08-01 00:00:00
abstract：:We describe herein a 61-year-old woman who presented with fever, night sweats and cough. The diagnosis of pneumonia was established, but with symptom recurrence following antibiotic therapy, further diagnostics were performed. Biopsy via bronchoscopy revealed cryptogenic organizing pneumonia, and later on follow-up, a...
journal_title：Immunologic research
pub_type： 杂志文章
doi：10.1007/s12026-014-8571-7
更新日期：2014-12-01 00:00:00
abstract：:The initial stages of an immune response are regulated at the level of the cell-surface antigen and Fc receptors. The extracellular portions of these receptors provide immune specificity and determine the nature of the responding effector cells, whereas the intracellular portion transduces signals into the cell and de...
journal_title：Immunologic research
pub_type： 杂志文章,评审
doi：10.1007/BF02786325
更新日期：1997-02-01 00:00:00
abstract：:The endoplasmic reticulum aminopeptidase 1 (ERAP1) performs a major role in antigen processing, trimming N-terminally extended peptides to the final epitope for presentation by major histocompatibility complex class I molecules. Recent genome-wide association studies have identified single nucleotide polymorphisms (SN...
journal_title：Immunologic research
pub_type： 杂志文章,评审
doi：10.1007/s12026-014-8576-2
更新日期：2014-12-01 00:00:00
abstract：:Studies on the biologic and molecular genetic underpinnings of multiple myeloma (MM) have identified the pleiotropic, pro-inflammatory cytokine, interleukin-6 (IL-6), as a factor crucial to the growth, proliferation and survival of myeloma cells. IL-6 is also a potent stimulator of osteoclastogenesis and a sculptor of...
journal_title：Immunologic research
pub_type： 杂志文章,评审
doi：10.1007/s12026-014-8528-x
更新日期：2014-08-01 00:00:00
abstract：:The generation and maintenance of B lymphocytes is controlled by biochemical signals transmitted by the B cell antigen receptor(BCR) complex. These signals are transduced by multiple cytoplasmic protein tyrosine kinases (PTKs) including Lyn, Syk, and Bruton's tyrosine kinase (BTK). Upon BCR engagement, these PTKs acti...
journal_title：Immunologic research
pub_type： 杂志文章,评审
doi：10.1385/IR:23:2-3:147
更新日期：2001-01-01 00:00:00
abstract：:Invariant CD1d-restricted natural killer T (iNKT) cells function during innate and adaptive immune responses. A functional and numerical deficiency of iNKT cells is well documented in both nonobese diabetic (NOD) mice and humans with autoimmune type 1 diabetes (T1D). Restoring the numerical and/or functional deficienc...
journal_title：Immunologic research
pub_type： 杂志文章,评审
doi：10.1385/IR:31:3:177
更新日期：2005-01-01 00:00:00
abstract：:Human α-fucosidase (EC 3.2.1.51) is an enzyme (hydrolase) of particular biological and medical interest, as the inherited deficiency in its activity leads to fucosidosis, a pathology belonging to severe glycoprotein lysosomal storage disorders. Although its importance has increased in latest years, data about its plas...
journal_title：Immunologic research
pub_type： 杂志文章
doi：10.1007/s12026-017-8943-x
更新日期：2017-10-01 00:00:00
abstract：:During thymocyte development bone marrow-derived precursors in the thymus undergo a series of differentiation steps to produce self-tolerant, mature T lymphocytes. The thymus contains two functionally distinct anatomical compartments, consisting of a centrally located medulla surrounded by the thymic cortex. These com...
journal_title：Immunologic research
pub_type： 杂志文章,评审
doi：10.1007/s12026-012-8301-y
更新日期：2012-12-01 00:00:00
abstract：:Staphylococcal exotoxins, staphylococcal enterotoxins A-E (SEA-SEE), and toxic shock syndrome toxin- (TSST-1) are potent activators of the immune system and cause a variety of diseases in humans, ranging from food poisoning to shock. These toxins are called superantigens because of their ability to polyclonally activa...
journal_title：Immunologic research
pub_type： 杂志文章,评审
doi：10.1007/BF02786471
更新日期：1999-01-01 00:00:00
abstract：:Severe combined immunodeficiency (SCID) disorders compromise lymphocyte numbers and/or function. One subset of SCID typically affects T cell and Natural Killer (NK) cell development in tandem (T-B+NK-) due to mutations arising in the genes encoding the common γ chain or Janus Kinase 3 (JAK3). In rare circumstances, mu...
journal_title：Immunologic research
pub_type： 杂志文章
doi：10.1007/s12026-020-09123-x
更新日期：2020-02-01 00:00:00
abstract：:B cell development starts in the bone marrow where hematopoietic stem cells (HSCs) progress through sequential developmental stages, as it differentiates into a naïve B cell expressing surface immunoglobulin. In the periphery, B cells that encounter antigen can further differentiate into antibody-secreting plasma cell...
journal_title：Immunologic research
pub_type： 杂志文章,评审
doi：10.1007/s12026-011-8225-y
更新日期：2011-08-01 00:00:00
abstract：:The two-signal model of T cell activation states that antigen recognition by TCR provides a tolerogenic signal (termed Signal 1) unless the T cell receives simultaneous costimulation (Signal 2) that permits antigen recognition to prime activation. Our efforts to characterize genetic and biochemical factors resulting f...
journal_title：Immunologic research
pub_type： 杂志文章,评审
doi：10.1007/s12026-009-8147-0
更新日期：2010-07-01 00:00:00
abstract：:Long noncoding RNAs (lncRNA) play key roles in regulating autoimmunity and immunity balance. LncRNA TMEVPG1, which is encoded by a gene located near the Ifn gene, contributes to interferon gamma expression. We investigated the expression of TMEVPG1 in patients with Sjögren syndrome (SS) to determine its role in the pa...
journal_title：Immunologic research
pub_type： 杂志文章
doi：10.1007/s12026-015-8715-4
更新日期：2016-04-01 00:00:00
abstract：:Contact hypersensitivity (CHS) is a T cell-mediated immune response to cutaneous sensitization and subsequent challenge with haptens such as dinitrofluorobenzene and oxazolone. Many aspects concerning the development and regulation of CHS remain unknown. Using CHS as a model of T cell-mediated immune responses to anti...
journal_title：Immunologic research
pub_type： 杂志文章,评审
doi：10.1385/IR:24:1:69
更新日期：2001-01-01 00:00:00
