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Journal of Leukocyte Biology

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https://www.readbyqxmd.com/read/28292946/nox2-dependent-immunosuppression-in-chronic-myelomonocytic-leukemia
#1
Johan Aurelius, Alexander Hallner, Olle Werlenius, Rebecca Riise, Lars Möllgård, Mats Brune, Markus Hansson, Anna Martner, Fredrik B Thorén, Kristoffer Hellstrand
Chronic myelomonocytic leukemia (CMML) is a myeloproliferative and myelodysplastic neoplasm with few treatment options and dismal prognosis. The role of natural killer (NK) cells and other antileukemic lymphocytes in CMML is largely unknown. We aimed to provide insight into the mechanisms of immune evasion in CMML with a focus on immunosuppressive reactive oxygen species (ROS) formed by the myeloid cell NADPH oxidase-2 (NOX2). The dominant population of primary human CMML cells was found to express membrane-bound NOX2 and to release ROS, which, in turn, triggered extensive PARP-1-dependent cell death in cocultured NK cells, CD8(+) T effector memory cells, and CD8(+) T effector cells...
March 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28292945/from-leukocyte-recruitment-to-resolution-of-inflammation-the-cardinal-role-of-integrins
#2
REVIEW
Ioannis Kourtzelis, Ioannis Mitroulis, Janusz von Renesse, George Hajishengallis, Triantafyllos Chavakis
Integrins constitute a large group of adhesion receptors that are formed as heterodimers of α and β subunits. Their presence and activation status on the surface of leukocytes modulate a broad spectrum of processes in inflammation and immunity. This mini review critically outlines research advances with regard to the function of leukocyte integrins in regulating and integrating the onset and resolution of acute inflammation. Specifically, we summarize and discuss relevant, current literature that supports the multifunctional role of integrins and their partners...
March 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28292944/the-mazy-case-of-notch-and-immunoregulatory-cells
#3
REVIEW
Paola Grazioli, Maria Pia Felli, Isabella Screpanti, Antonio Francesco Campese
The Notch pathway represents a conserved signal transduction machinery that is straightforward and based on a few elements (ligands, receptors, transducers). However, the existence of multiple control levels of the Notch signaling final outcome makes it strictly context dependent and dose dependent. The function of Notch as a regulator of cell development and differentiation, as well as the aberrant consequences of its modulation, either positive or negative, is well established. In this review, we will discuss our current knowledge about Notch-dependent regulation of generation and function of 2 subsets of the immunoregulatory system, namely regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs)...
March 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28283665/il-18-dependent-nkg2d-ligand-upregulation-on-accessory-cells-is-mediated-by-the-pi3k-gsk-3-pathway
#4
Joshua D Brandstadter, Huiyao Chen, Songfu Jiang, Xiaopei Huang, Yiping Yang
NK cells are critical for the control of viral infections. Studies have shown that efficient NK cell activation in response to infection with VV in vivo requires multiple pathways, including the NKG2D pathway. We have recently shown that IL-18 is necessary for the activation of NK cells through upregulation of the NKG2D ligand Rae-1 on DCs upon VV infection. However, how IL-18R signaling on the accessory cells contributes to Rae-1 up-regulation remains to be defined. In this study, we found IL-18-mediated Rae-1 up-regulation in accessory cells, including macrophages and DCs, to be dependent on the MyD88-PI3K pathway...
March 10, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28274991/macrophage-derived-apoptotic-bodies-promote-the-proliferation-of-the-recipient-cells-via-shuttling-microrna-221-222
#5
Ziwen Zhu, Duo Zhang, Heedoo Lee, Aravind Ajakumar Menon, Jingxuan Wu, Kebin Hu, Yang Jin
Bacterial pneumonia is a common and serious clinical entity. Alveolar epithelial cells and alveolar macrophages are the first line of defense in the innate immunity against bacterial pathogens. Epithelial cells are known to release chemokines/cytokines that recruit and activate phagocytic cells. However, the signals sent from alveolar macrophages back to the lung epithelial cells remain largely unexplored. We found that LPS, a well-recognized stimulator derived from gram-negative (G(-)) bacteria, rapidly and robustly induces the secretion of macrophage-derived extracellular vesicles (EVs)...
March 8, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28270408/phenotypic-and-functional-consequences-of-different-isolation-protocols-on-skin-mononuclear-phagocytes
#6
Rachel A Botting, Kirstie M Bertram, Heeva Baharlou, Kerrie J Sandgren, James Fletcher, Jake W Rhodes, Hafsa Rana, Toby M Plasto, Xin Maggie Wang, Jake J K Lim, Laith Barnouti, Mark P Kohout, Tim Papadopoulos, Steve Merten, Norman Olbourne, Anthony L Cunningham, Muzlifah Haniffa, Andrew N Harman
Mononuclear phagocytes are present in skin and mucosa and represent one of the first lines of defense against invading pathogens, which they detect via an array of pathogen-binding receptors expressed on their surface. However, their extraction from tissue is difficult, and the isolation technique used has functional consequences on the cells obtained. Here, we compare mononuclear phagocytes isolated from human skin using either enzymatic digestion or spontaneous migration. Cells isolated via enzymatic digestion are in an immature state, and all subsets are easily defined...
March 7, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28264904/neutrophils-as-active-regulators-of-the-immune-system-in-the-tumor-microenvironment
#7
REVIEW
Merav E Shaul, Zvi G Fridlender
In recent years, the role of immune cells in tumor progression has been a matter of increasing interest. Neutrophils constitute an important portion of the immune cells infiltrating the tumor microenvironment. Traditionally viewed as the first line of defense against infections, it is now well accepted that neutrophils also have an important role in multiple aspects of cancer biology. Multiple and heterogeneous neutrophil subsets have been identified in tumors and in circulation. Evidence from many studies now supports the notion that tumor-associated neutrophils (TANs) show functional plasticity driven by multiple factors present in the tumor microenvironment...
March 6, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28258153/rationalized-design-of-a-mucosal-vaccine-protects-against-mycobacterium-tuberculosis-challenge-in-mice
#8
Mushtaq Ahmed, Hongmei Jiao, Racquel Domingo-Gonzalez, Shibali Das, Kristin L Griffiths, Javier Rangel-Moreno, Uma M Nagarajan, Shabaana A Khader
Pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is a leading cause of global morbidity and mortality. The only licensed TB vaccine, Mycobacterium bovis bacillus Calmette-Guerin (BCG), has variable efficacy in protecting against pulmonary TB. Thus, the development of more effective TB vaccines is critical to control the TB epidemic. Specifically, vaccines delivered through the mucosal route are known to induce Th17 responses and provide superior protection against Mtb infection. However, already tested Th17-inducing mucosal adjuvants, such as heat-labile enterotoxins and cholera toxins, are not considered safe for use in humans...
March 3, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28258152/chemical-composition-and-phagocyte-immunomodulatory-activity-of-ferula-iliensis-essential-oils
#9
Gulmira Özek, Igor A Schepetkin, Gulzhakhan A Utegenova, Liliya N Kirpotina, Spencer R Andrei, Temel Özek, Kemal Hüsnü Can Başer, Karime T Abidkulova, Svetlana V Kushnarenko, Andrei I Khlebnikov, Derek S Damron, Mark T Quinn
Essential oil extracts from Ferula iliensis have been used traditionally in Kazakhstan for treatment of inflammation and other illnesses. Because little is known about the biologic activity of these essential oils that contributes to their therapeutic properties, we analyzed their chemical composition and evaluated their phagocyte immunomodulatory activity. The main components of the extracted essential oils were (E)-propenyl sec-butyl disulfide (15.7-39.4%) and (Z)-propenyl sec-butyl disulfide (23.4-45.0%)...
March 3, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28254841/stat5-phosphorylation-in-cd4-t-cells-from-patients-with-sle-is-related-to-changes-in-their-subsets-and-follow-up-disease-severity
#10
Aleš Goropevšek, Maksimiljan Gorenjak, Suzana Gradišnik, Klara Dai, Iztok Holc, Radovan Hojs, Ivan Krajnc, Artur Pahor, Tadej Avčin
Activation of the STAT5 signaling pathway up-regulates antiapoptotic protein Bcl2 and drives proliferation of autoreactive conventional CD4 T cells (Tcons). In systemic lupus erythematosus (SLE), an increased T cell Bcl2 content and perturbed homeostasis of CD45RA(-)FOXP3(hi) activated regulatory T cells (aTregs) were described. We assessed Tcon/Treg subsets and phosphorylation of STAT5 (pSTAT5) in blood T cells from patients with SLE by using conventional and imaging flow cytometry. Forty-one patients with SLE, 33 healthy controls, and 29 patients with rheumatoid arthritis were included...
March 2, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28254840/extracellular-matrix-and-the-myeloid-in-myeloma-compartment-balancing-tolerogenic-and-immunogenic-inflammation-in-the-myeloma-niche
#11
REVIEW
Fotis Asimakopoulos, Chelsea Hope, Michael G Johnson, Adam Pagenkopf, Kimberly Gromek, Bradley Nagel
The last 10-15 years have witnessed a revolution in treating multiple myeloma, an incurable cancer of Ab-producing plasma cells. Advances in myeloma therapy were ushered in by novel agents that remodel the myeloma immune microenvironment. The first generation of novel agents included immunomodulatory drugs (thalidomide analogs) and proteasome inhibitors that target crucial pathways that regulate immunity and inflammation, such as NF-κB. This paradigm continued with the recent regulatory approval of mAbs (elotuzumab, daratumumab) that impact both tumor cells and associated immune cells...
March 2, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28250011/microglia-driven-regulation-of-oligodendrocyte-lineage-cells-myelination-and-remyelination
#12
REVIEW
Veronique E Miron
Microglia are the resident macrophages of the CNS and members of the innate immune system. As such, they serve important functions in surveillance for indicators of damage and subsequent initiation of an inflammatory response. Although often implicated in neural damage, recent studies have also suggested beneficial roles of activated microglia and inflammation in developmental and regenerative processes in the CNS. These include regulating events leading to the generation and regeneration of myelin, the insulation surrounding nerve fibers which is critical for nerve health and function...
March 1, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28242623/type-i-interferon-enhanced-il-10-expression-in-human-cd4-t-cells-is-regulated-by-stat3-stat2-and-batf-transcription-factors
#13
Umeshree Govender, Béatrice Corre, Yasmine Bourdache, Sandra Pellegrini, Frédérique Michel
Type I IFN can exert pro- and anti-inflammatory activities in the immune system. Here, we have investigated the mechanism by which IFN-α enhances early expression of the anti-inflammatory cytokine IL-10 in human CD45RA(+)CD4(+) T cells. With the use of transcriptomic and biochemical approaches, we found distinct and combined contributions of the IFN and the TCR signaling pathways to the induction of STAT1/2/3 and the basic leucine zipper activating transcription factor-like (BATF) family members. Moreover, IFN-induced STAT3 phosphorylation was prolonged by the TCR response, whereas IFN-induced STAT2 phosphorylation was of long duration...
February 27, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28235774/development-of-platelets-during-steady-state-and-inflammation
#14
REVIEW
Gerhard Müller-Newen, Matthias B Stope, Thomas Kraus, Patrick Ziegler
Megakaryocytes (MK) are the sole source of platelets in the body. They develop from lineage-committed hematopoietic stem and progenitor cells (HSPCs) via intermediate cells, which differ in morphology, size, ploidy, and surface phenotype. Development and maturation of MKs is governed by different transcription factors, including GATA-1, E26 transformation-specific transcription factor (ETS) family members, nuclear factor erythroid 2 transcription factor (NF-E2), and STAT3. During such challenges as acute inflammation, platelets are consumed in high numbers and must be replenished to secure survival of the host...
February 24, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28235773/tlr10-suppresses-the-activation-and-differentiation-of-monocytes-with-effects-on-dc-mediated-adaptive-immune-responses
#15
Nicholas J Hess, Christopher Felicelli, Jennifer Grage, Richard I Tapping
TLRs are important pattern-recognition receptors involved in the activation of innate immune responses against foreign pathogens. TLR10 is the only TLR family member without a known ligand, signaling pathway, or clear cellular function. Previous work has shown that TLR10 suppresses proinflammatory cytokine production in response to TLR agonists in a mixed human mononuclear cell population. We report that TLR10 is preferentially expressed on monocytes and suppresses proinflammatory cytokine production resulting from either TLR or CD40 stimulation...
February 24, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28235772/frontline-science-shh-production-and-gli-signaling-is-activated-in-vivo-in-lung-enhancing-the-th2-response-during-a-murine-model-of-allergic-asthma
#16
Ariane S I Standing, Diana C Yánez, Rosie Ross, Tessa Crompton, Anna L Furmanski
The pathophysiology of allergic asthma is driven by Th2 immune responses after aeroallergen inhalation. The mechanisms that initiate, potentiate, and regulate airway allergy are incompletely characterized. We have shown that Hh signaling to T cells, via downstream Gli transcription factors, enhances T cell conversion to a Th2 phenotype. In this study, we showed for the first time, to our knowledge, that Gli-dependent transcription is activated in T cells in vivo during murine AAD, a model for the immunopathology of asthma, and that genetic repression of Gli signaling in T cells decreases the differentiation and recruitment of Th2 cells to the lung...
February 24, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28235771/dynamics-of-myeloid-cell-populations-during-relapse-preventive-immunotherapy-in-acute-myeloid-leukemia
#17
Anna Rydström, Alexander Hallner, Johan Aurelius, Frida Ewald Sander, Elin Bernson, Roberta Kiffin, Fredrik Bergh Thoren, Kristoffer Hellstrand, Anna Martner
Relapse of leukemia in the postchemotherapy phase contributes to the poor prognosis and survival in patients with acute myeloid leukemia (AML). In an international phase IV trial (ClinicalTrials.gov; NCT01347996), 84 patients with AML in first complete remission who had not undergone transplantation received immunotherapy with histamine dihydrochloride (HDC) and low-dose IL-2 with the aim of preventing relapse. The dynamics of myeloid cell counts and expression of activation markers was assessed before and after cycles of immunotherapy and correlated with clinical outcome in terms of relapse risk and survival...
February 24, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28232386/different-dynamics-of-nlrp3-inflammasome-mediated-il%C3%A2-1%C3%AE-production-in-gm-csf-and-m-csf-differentiated-human-macrophages
#18
Marietta Margit Budai, József Tőzsér, Szilvia Benkő
IL-1β is a "master" cytokine regulating a wide variety of physiologic and immunologic processes. The most frequently studied models for NLRP3 inflammasome-mediated IL-1β production are the macrophages; however, depending on their microenvironment, they can develop into functionally different cells. Several protocols have been developed to model the diversity of these cells in vitro. Here, we report for the first time, to our knowledge, a comparative study about the dynamics and molecular mechanisms of NLRP3 inflammasome priming and activation in LPS-stimulated, human, monocyte-derived GM- or M-macrophages, differentiated in the presence of GM-CSF or M-CSF, respectively...
February 23, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28223316/energy-metabolism-drives-myeloid-derived-suppressor-cell-differentiation-and-functions-in-pathology
#19
REVIEW
Antonio Sica, Laura Strauss
Over the last decade, a heterogeneous population of immature myeloid cells with major regulatory functions has been described in cancer and other pathologic conditions and ultimately defined as MDSCs. Most of the early work on the origins and functions of MDSCs has been in murine and human tumor bearers in which MDSCs are known to be immunosuppressive and to result in both reduced immune surveillance and antitumor cytotoxicity. More recent studies, however, suggest that expansion of these immature myeloid cells may be linked to most, if not all, chronic and acute inflammatory processes...
February 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28196851/inhibition-of-lipopolysaccharide-induced-osteoclast-formation-and-bone-resorption-in-vitro-and-in-vivo-by-cysteine-proteinase-inhibitors
#20
Fredrik Strålberg, Ali Kassem, Franciszek Kasprzykowski, Magnus Abrahamson, Anders Grubb, Catharina Lindholm, Ulf H Lerner
Inflammation-induced bone destruction is a major treatment target in many inflammatory skeletal diseases. The aim of this study was to investigate if the cysteine proteinase inhibitors cystatin C, fungal cysteine proteinase inhibitor (E-64), and N-benzyloxycarbonyl-arginyl-leucyl-valyl-glycyl-diazomethane acetate (Z-RLVG-CHN2) can inhibit LPS-induced osteoclast formation. Mouse bone marrow macrophages (BMMs) were isolated and primed with receptor activator of NF-κB ligand (RANKL) for 24 h, followed by stimulation with LPS, with and without inhibitors...
February 14, 2017: Journal of Leukocyte Biology
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