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https://www.readbyqxmd.com/read/28098193/non-pathogenic-tissue-resident-cd8-t-cells-uniquely-accumulate-in-the-brains-of-lupus-prone-mice
#1
Peter A Morawski, Chen-Feng Qi, Silvia Bolland
Severe lupus often includes psychiatric and neurological sequelae, although the cellular contributors to CNS disease remain poorly defined. Using intravascular staining to discriminate tissue-localized from blood-borne cells, we find substantial accumulation of CD8(+) T cells relative to other lymphocytes in brain tissue, which correlates with lupus disease and limited neuropathology. This is in contrast to all other affected organs, where infiltrating CD4(+) cells are predominant. Brain-infiltrating CD8(+) T cells represent an activated subset of those found in the periphery, having a resident-memory phenotype (CD69(+)CD122(-)PD1(+)CD44(+)CD62L(-)) and expressing adhesion molecules (VLA-4(+)LFA-1(+)) complementary to activated brain endothelium...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28077302/neutrophil-adhesion-and-crawling-dynamics-on-liver-sinusoidal-endothelial-cells-under-shear-flow
#2
Hao Yang, Ning Li, Yu Du, Chunfang Tong, Shouqin Lü, Jinrong Hu, Yan Zhang, Mian Long
Neutrophil (polymorphonuclear leukocyte, PMN) recruitment in the liver sinusoid takes place in almost all liver diseases and contributes to pathogen clearance or tissue damage. While PMN rolling unlikely appears in liver sinusoids and Mac-1 or CD44 is assumed to play respective roles during in vivo local or systematic inflammatory stimulation, the regulating mechanisms of PMN adhesion and crawling dynamics are still unclear from those in vivo studies. Here we developed a two-dimensional in vitro sinusoidal model with primary liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs) to investigate TNF-α-induced PMN recruitment under shear flow...
January 8, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28066794/altered-monocyte-and-endothelial-cell-adhesion-molecule-expression-is-linked-to-vascular-inflammation-in-human-immunodeficiency-virus-infection
#3
Manjusha Kulkarni, Emily Bowman, Janelle Gabriel, Taylor Amburgy, Elizabeth Mayne, David A Zidar, Courtney Maierhofer, Abigail Norris Turner, Jose A Bazan, Susan L Koletar, Michael M Lederman, Scott F Sieg, Nicholas T Funderburg
BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals have increased risk for vascular thrombosis, potentially driven by interactions between activated leukocytes and the endothelium. METHODS: Monocyte subsets (CD14(+)CD16(-), CD14(+)CD16(+), CD14(Dim)CD16(+)) from HIV negative (HIV(-)) and antiretroviral therapy-treated HIV positive (HIV(+)) participants (N = 19 and 49) were analyzed by flow cytometry for adhesion molecule expression (lymphocyte function-associated antigen 1 [LFA-1], macrophage-1 antigen [Mac-1], CD11c/CD18, very late antigen [VLA]-4) and the fractalkine receptor (CX3CR1); these receptors recognize ligands (intercellular adhesion molecules [ICAMs], vascular cell adhesion molecule [VCAM]-1, fractalkine) on activated endothelial cells (ECs) and promote vascular migration...
October 2016: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28058622/lifitegrast-ophthalmic-solution-5-a-review-in-dry-eye-disease
#4
Gillian M Keating
Lifitegrast is a novel small molecule integrin antagonist that blocks the binding of intercellular adhesion molecule 1 (ICAM-1) to lymphocyte function-associated antigen 1 (LFA-1). Lifitegrast ophthalmic solution 5% (Xiidra™) was recently approved in the USA for the treatment of dry eye disease. The efficacy of lifitegrast ophthalmic solution 5% was compared with vehicle in a 12-week phase 2 study and three 12-week phase 3 studies (OPUS-1, OPUS-2 and OPUS-3) in patients with dry eye disease. Taken as a whole, results of these trials support the treatment effect of lifitegrast ophthalmic solution 5% in improving a symptom of dry eye disease (i...
January 6, 2017: Drugs
https://www.readbyqxmd.com/read/28052935/d120-and-k152-within-the-ph-domain-of-t-cell-adapter-skap55-regulate-plasma-membrane-targeting-of-skap55-and-lfa-1-affinity-modulation-in-human-t-lymphocytes
#5
Amelie Witte, Bernhard Meineke, Jana Sticht, Lars Philipsen, Benno Kuropka, Andreas J Müller, Christian Freund, Burkhart Schraven, Stefanie Kliche
The β2-integrin lymphocyte function-associated antigen-1 (LFA-1) is needed for T cell receptor (TCR) induced activation of LFA-1 to promote T cell adhesion and interaction with antigen presenting cells (APCs). LFA-1-mediated cell-cell interactions are critical for proper T cell differentiation and proliferation. The Src Kinase-Associated Phosphoprotein of 55 kDa (SKAP55) is a key regulator of TCR-mediated LFA-1 signaling (inside-out/outside-in signaling). To gain understanding of how SKAP55 controls TCR-mediated LFA-1 activation, we assessed the functional role of its Pleckstrin Homology (PH) domain...
January 4, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28003439/prolonged-exposure-to-volatile-anesthetic-isoflurane-worsens-the-outcome-of-polymicrobial-abdominal-sepsis
#6
Sophia Koutsogiannaki, Matthew M Schaefers, Toshiaki Okuno, Mai Ohba, Takehiko Yokomizo, Gregory P Priebe, James A DiNardo, Soriano G Sulpicio, Koichi Yuki
Sepsis continues to result in high morbidity and mortality. General anesthesia is often administered to septic patients, but the impacts of general anesthesia on host defense are not well understood. General anesthesia can be given by volatile and intravenous anesthetics. Our previous in vitro study showed that volatile anesthetic isoflurane directly inhibits leukocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1), critical adhesion molecules on leukocytes. Thus, the role of isoflurane exposure on in vivo LFA-1 and Mac-1 function was examined using polymicrobial abdominal sepsis model in mice...
December 20, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27986909/sos1-arhgef1-and-dock2-rho-gefs-mediate-jak-dependent-lfa-1-activation-by-chemokines
#7
Lara Toffali, Alessio Montresor, Michela Mirenda, Giorgio Scita, Carlo Laudanna
JAK-dependent activation of the rho module of integrin affinity triggering mediates chemokine-induced leukocyte adhesion. However, the signaling events linking JAKs to rho small GTPase activation by chemokines is still incompletely described. In this study, we show that son of sevenless 1 (SOS1), rho guanine nucleotide exchange factor (GEF)1 (ARHGEF1), and dedicator of cytokinesis (DOCK)2 GEFs mediate CXCL12-induced LFA-1 activation in human primary T lymphocytes. Downregulated expression of SOS1, ARHGEF1, and DOCK2 impairs LFA-1-mediated rapid T lymphocyte adhesion as well as underflow arrest on ICAM-1 induced by CXCL12...
December 16, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27965383/defects-in-cd4-t-cell-lfa-1-integrin-dependent-adhesion-and-proliferation-protect-cd47-mice-from-eae
#8
Veronica Azcutia, Ribal Bassil, Jan M Herter, Daniel Engelbertsen, Gail Newton, Anu Autio, Tanya Mayadas, Andrew H Lichtman, Samia J Khoury, Charles A Parkos, Wassim Elyaman, Francis W Luscinskas
CD47 is known to play an important role in CD4(+) T cell homeostasis. We recently reported a reduction in mice deficient in the Cd47 gene (Cd47(-/-)) CD4(+) T cell adhesion and transendothelial migration (TEM) in vivo and in vitro as a result of impaired expression of high-affinity forms of LFA-1 and VLA-4 integrins. A prior study concluded that Cd47(-/-) mice were resistant to experimental autoimmune encephalomyelitis (EAE) as a result of complete failure in CD4(+) T cell activation after myelin oligodendrocyte glycoprotein peptide 35-55 aa (MOG35-55) immunization...
December 13, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27956903/comprehensive-screening-of-cell-surface-markers-expressed-by-adult-derived-human-liver-stem-progenitor-cells-harvested-at-passage-5-potential-implications-for-engraftment
#9
Pierre-Edouard Dollet, Joachim Ravau, Floriane André, Mustapha Najimi, Etienne Sokal, Catherine Lombard
Mesenchymal stromal cells (MSCs) are known to have potential therapeutic benefits for a number of diseases. However, many studies report low engraftment levels, regardless of the target organ. One possible explanation could be that MSCs do not express the necessary receptors for engraftment. Indeed, MSCs appear to use a similar mechanism to leukocytes to engraft into injured organs, relying on various receptors for rolling, firm adhesion, and transmigration. In this study, we conducted an extensive surface molecule screening of adult-derived human liver stem/progenitor cells (ADHLSC) in an attempt to shed some light on this subject...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27941787/recruitment-of-calcineurin-to-the-tcr-positively-regulates-t-cell-activation
#10
Debjani Dutta, Valarie A Barr, Itoro Akpan, Paul R Mittelstadt, Laishram I Singha, Lawrence E Samelson, Jonathan D Ashwell
Calcineurin is a phosphatase whose primary targets in T cells are NFAT transcription factors, and inhibition of calcineurin activity by treatment with cyclosporin A (CsA) or FK506 is a cornerstone of immunosuppressive therapies. Here we found that calcineurin was recruited to the T cell antigen receptor (TCR) signaling complex, where it reversed inhibitory phosphorylation of the tyrosine kinase Lck on Ser59 (Lck(S59)). Loss of calcineurin activity impaired phosphorylation of Tyr493 of the tyrosine kinase ZAP-70 (ZAP-70(Y493)), as well as some downstream pathways in a manner consistent with signaling in cells expressing Lck(S59A) (Lck that cannot be phosphorylated) or Lck(S59E) (a phosphomimetic mutant)...
December 12, 2016: Nature Immunology
https://www.readbyqxmd.com/read/27940100/the-effect-of-different-anesthetics-on-tumor-cytotoxicity-by-natural-killer-cells
#11
Kazumasa Tazawa, Sophia Koutsogiannaki, Matthew Chamberlain, Koichi Yuki
A number of retrospective studies have suggested that choice of anesthetic drugs during surgical tumor resection might affect tumor recurrence/metastasis, or outcome of patients. The recent study showed that volatile anesthetics-based general anesthesia was associated with the worse outcomes than intravenous anesthetics-based general anesthesia. However, the underlying mechanism is yet to be determined. Because natural killer (NK) cells are implicated as important immune cells for tumor recurrence/metastasis in the perioperative period, we examined the effect of different anesthetics on NK cell-mediated tumor cytotoxicity...
January 15, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/27915019/the-impact-of-cell-surface-pegylation-and-short-course-immunotherapy-on-islet-graft-survival-in-an-allogeneic-murine-model
#12
Jaime A Giraldo, R Damaris Molano, Hernán R Rengifo, Carmen Fotino, Kerim M Gattás-Asfura, Antonello Pileggi, Cherie L Stabler
: Islet transplantation is a promising therapy for Type 1 diabetes mellitus; however, host inflammatory and immune responses lead to islet dysfunction and destruction, despite potent systemic immunosuppression. Grafting of poly(ethylene glycol) (PEG) to the periphery of cells or tissues can mitigate inflammation and immune recognition via generation of a steric barrier. Herein, we sought to evaluate the complementary impact of islet PEGylation with a short-course immunotherapy on the survival of fully-MHC mismatched islet allografts (DBA/2 islets into diabetic C57BL/6J recipients)...
November 30, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27907215/cd8-t-cells-induce-fatal-brainstem-pathology-during-cerebral-malaria-via-luminal-antigen-specific-engagement-of-brain-vasculature
#13
Phillip A Swanson, Geoffrey T Hart, Matthew V Russo, Debasis Nayak, Takele Yazew, Mirna Peña, Shahid M Khan, Chris J Janse, Susan K Pierce, Dorian B McGavern
Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection that results in thousands of deaths each year, mostly in African children. The in vivo mechanisms underlying this fatal condition are not entirely understood. Using the animal model of experimental cerebral malaria (ECM), we sought mechanistic insights into the pathogenesis of CM. Fatal disease was associated with alterations in tight junction proteins, vascular breakdown in the meninges / parenchyma, edema, and ultimately neuronal cell death in the brainstem, which is consistent with cerebral herniation as a cause of death...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27906544/lfa-1-icam-1-interaction-as-a-therapeutic-target-in-dry-eye-disease
#14
Stephen C Pflugfelder, Michael Stern, Steven Zhang, Amir Shojaei
Dry eye disease (DED) is a common ocular disorder associated with inflammation of the lacrimal gland and ocular surface. The interaction of the integrin lymphocyte function-associated antigen-1 (LFA-1) with its cognate ligand intercellular adhesion molecule-1 (ICAM-1) is known to have important roles in the interaction of a variety of cells involved in immune responses and inflammation, including those prominent in ocular surface inflammation. Lifitegrast, an LFA-1 antagonist that blocks binding of ICAM-1 to LFA-1, has recently been approved in the United States for the treatment of signs and symptoms of DED...
January 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27888551/selective-targeting-of-high-affinity-lfa-1-does-not-augment-costimulation-blockade-in-a-nonhuman-primate-renal-transplantation-model
#15
K P Samy, D A Anderson, D J Lo, M S Mulvihill, M Song, A B Farris, B S Parker, A L MacDonald, C Lu, T A Springer, S C Kachlany, K A Reimann, T How, F V Leopardi, K S Franke, K D Williams, B H Collins, A D Kirk
Costimulation blockade (CoB) via belatacept is a lower morbidity alternative to calcineurin inhibitor (CNI)-based immunosuppression. However, it has higher rates of early acute rejection. These early rejections are mediated in part by memory T cells, which have reduced dependence on the pathway targeted by belatacept, and increased adhesion molecule expression. One such molecule is Leukocyte Function Associated Antigen (LFA)-1. LFA-1 exists in two forms, a commonly expressed, low-affinity form, and a transient, high-affinity form, expressed only during activation...
November 26, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27883115/lifitegrast-first-lfa-1-icam-1-antagonist-for-treatment-of-dry-eye-disease
#16
D M Paton
Dry eye disease is an extremely common condition affecting millions worldwide. The underlying pathophysiological mechanism is thought to be localized inflammation of the ocular surface resulting in the localization of T cells at this surface followed by their activation and subsequent liberation of cytokines. This effect on T cells results from the binding of lymphocyte function-associated antigen-1 (LFA-1) located on T cells to intercellular adhesion molecule 1 (ICAM-1) expressed on inflamed epithelium and endothelium, and on T cells...
September 2016: Drugs of Today
https://www.readbyqxmd.com/read/27844285/th17-cells-induce-dopaminergic-neuronal-death-via-lfa-1-icam-1-interaction-in-a-mouse-model-of-parkinson-s-disease
#17
Zhan Liu, Yan Huang, Bei-Bei Cao, Yi-Hua Qiu, Yu-Ping Peng
T helper (Th)17 cells, a subset of CD4(+) T lymphocytes, have strong pro-inflammatory property and appear to be essential in the pathogenesis of many inflammatory diseases. However, the involvement of Th17 cells in Parkinson's disease (PD) that is characterized by a progressive degeneration of dopaminergic (DAergic) neurons in the nigrostriatal system is unclear. Here, we aimed to demonstrate that Th17 cells infiltrate into the brain parenchyma and induce neuroinflammation and DAergic neuronal death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- or 1-methyl-4-phenylpyridinium (MPP(+))-induced PD models...
November 14, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27825159/injection-of-htert-transduced-endothelial-progenitor-cells-promotes-beneficial-aortic-changes-in-a-high-fat-dietary-model-of-early-atherosclerosis
#18
Xingsheng Li, Yanru Deng, Shunrong Zhao, Dandan Zhang, Qingwei Chen
OBJECTIVES: Cultured endothelial progenitor cells (EPCs) display troubling issues that adversely affect their applicability to endothelial regeneration. We hypothesized that transduction of the human telomerase catalytic subunit (hTERT) gene would enhance EPC function in treating dietary-induced early atherosclerosis (AS). METHODS: A dietary-induced early AS model was successfully constructed in 90 healthy male rats, while 30 healthy control (HC) rats were normally fed...
November 9, 2016: Cardiology
https://www.readbyqxmd.com/read/27799367/formin-generated-actomyosin-arcs-propel-t-cell-receptor-microcluster-movement-at-the-immune-synapse
#19
Sricharan Murugesan, Jinsung Hong, Jason Yi, Dong Li, Jordan R Beach, Lin Shao, John Meinhardt, Grey Madison, Xufeng Wu, Eric Betzig, John A Hammer
Actin assembly and inward flow in the plane of the immunological synapse (IS) drives the centralization of T cell receptor microclusters (TCR MCs) and the integrin leukocyte functional antigen 1 (LFA-1). Using structured-illumination microscopy (SIM), we show that actin arcs populating the medial, lamella-like region of the IS arise from linear actin filaments generated by one or more formins present at the IS distal edge. After traversing the outer, Arp2/3-generated, lamellipodia-like region of the IS, these linear filaments are organized by myosin II into antiparallel concentric arcs...
November 7, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27760339/the-integrin-lfa-1-controls-t-follicular-helper-cell-generation-and-maintenance
#20
Alexandre P Meli, Ghislaine Fontés, Danielle T Avery, Scott A Leddon, Mifong Tam, Michael Elliot, Andre Ballesteros-Tato, Jim Miller, Mary M Stevenson, Deborah J Fowell, Stuart G Tangye, Irah L King
T follicular helper (Tfh) cells are a CD4(+) T cell subset critical for long-lived humoral immunity. We hypothesized that integrins play a decisive role in Tfh cell biology. Here we show that Tfh cells expressed a highly active form of leukocyte function-associated antigen-1 (LFA-1) that was required for their survival within the germinal center niche. In addition, LFA-1 promoted expression of Bcl-6, a transcriptional repressor critical for Tfh cell differentiation, and inhibition of LFA-1 abolished Tfh cell generation and prevented protective humoral immunity to intestinal helminth infection...
October 18, 2016: Immunity
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