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MyD88 in T cells

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https://www.readbyqxmd.com/read/28733470/dendritic-cell-targeted-lentiviral-vector-immunization-uses-pseudotransduction-and-dna-mediated-sting-and-cgas-activation
#1
Jocelyn T Kim, Yarong Liu, Rajan P Kulkarni, Kevin K Lee, Bingbing Dai, Geoffrey Lovely, Yong Ouyang, Pin Wang, Lili Yang, David Baltimore
Dendritic cell (DC) activation and antigen presentation are critical for efficient priming of T cell responses. Here, we study how lentiviral vectors (LVs) deliver antigen and activate DCs to generate T cell immunization in vivo. We report that antigenic proteins delivered in vector particles via pseudotransduction were sufficient to stimulate an antigen-specific immune response. The delivery of the viral genome encoding the antigen increased the magnitude of this response in vivo but was irrelevant in vitro...
July 21, 2017: Science Immunology
https://www.readbyqxmd.com/read/28697888/regulated-expansion-and-survival-of-chimeric-antigen-receptor-modified-t-cells-using-small-molecule-dependent-inducible-myd88-cd40
#2
Aaron E Foster, Aruna Mahendravada, Nicholas P Shinners, Wei-Chun Chang, Jeannette Crisostomo, An Lu, Mariam Khalil, Eva Morschl, Joanne L Shaw, Sunandan Saha, MyLinh T Duong, Matthew R Collinson-Pautz, David L Torres, Tania Rodriguez, Tsvetelina Pentcheva-Hoang, J Henri Bayle, Kevin M Slawin, David M Spencer
Anti-tumor efficacy of T cells engineered to express chimeric antigen receptors (CARs) is dependent on their specificity, survival, and in vivo expansion following adoptive transfer. Toll-like receptor (TLR) and CD40 signaling in T cells can improve persistence and drive proliferation of antigen-specific CD4(+) and CD8(+) T cells following pathogen challenge or in graft-versus-host disease (GvHD) settings, suggesting that these costimulatory pathways may be co-opted to improve CAR-T cell persistence and function...
July 8, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28680375/tlr-myd88-mediated-innate-immunity-in-intestinal-graft-versus-host-disease
#3
REVIEW
Young-Kwan Lee, Myungsoo Kang, Eun Young Choi
Graft-versus-host disease (GHVD) is a severe complication after allogeneic hematopoietic stem cell transplantation. The degree of inflammation in the gastrointestinal tract, a major GVHD target organ, correlates with the disease severity. Intestinal inflammation is initiated by epithelial damage caused by pre-conditioning irradiation. In combination with damages caused by donor-derived T cells, such damage disrupts the epithelial barrier and exposes innate immune cells to pathogenic and commensal intestinal bacteria, which release ligands for Toll-like receptors (TLRs)...
June 2017: Immune Network
https://www.readbyqxmd.com/read/28679988/follicular-lymphoma-with-plasmacytic-differentiation-accompanied-by-monoclonal-igg-gammopathy
#4
Tomomi Oka, Masayuki Kobayashi, Takaya Komori, Hirokazu Nakamine, Toshiyuki Kitano, Masakatsu Hishizawa, Tadakazu Kondoh, Kouhei Yamashita, Akifumi Takaori-Kondo
A 59-year-old woman presented with high serum total protein, detected on a screening examination. Laboratory tests revealed high plasma levels of M-protein (IgG-λ), and FDG-PET/CT revealed systemic lymph node swelling and a large tumorous mass in the abdominal cavity. Bone marrow aspirates contained 8.4% plasma cells and approximately 30% abnormal small lymphocytes. A biopsy of the left supraclavicular lymph node was initially interpreted as lymphoplasmacytic lymphoma (LPL). However, chromosomal analysis of the lymph node demonstrated an unusual karyotype with t (14;18) (q32;q21)...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28659358/b-cell-extrinsic-myd88-and-fcer1g-negatively-regulate-autoreactive-and-normal-b-cell-immune-responses
#5
Rebecca A Sweet, Kevin M Nickerson, Jaime L Cullen, Yujuan Wang, Mark J Shlomchik
MyD88 and FcR common γ-chain (Fcer1g, FcRγ) elicit proinflammatory responses to exogenous Ags. Deletion of these receptors in autoimmune models has generally led to reduced overall disease. In B cells, Myd88 is required for anti-DNA and anti-RNA autoantibody responses, whereas Fcer1g is not expressed in these cells. The roles of these receptors in myeloid cells during B cell autoimmune activation remain less clear. To investigate the roles of Myd88 and Fcer1g in non-B cells, we transferred anti-self-IgG (rheumatoid factor) B cells and their physiologic target Ag, anti-chromatin Ab, into mice lacking Fcer1g, Myd88, or both and studied the extrafollicular plasmablast response...
June 28, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28655469/transcutaneous-immunization-with-a-novel-imiquimod-nanoemulsion-induces-superior-t-cell-responses-and-virus-protection
#6
Pamela Aranda Lopez, Mark Denny, Ann-Kathrin Hartmann, Astrid Alflen, Hans Christian Probst, Esther von Stebut, Stefan Tenzer, Hansjörg Schild, Michael Stassen, Peter Langguth, Markus P Radsak
BACKGROUND: Transcutaneous immunization (TCI) is a novel vaccination strategy utilizing the skin associated lymphatic tissue to induce immune responses. TCI using a cytotoxic T lymphocyte (CTL) epitope and the Toll-like receptor 7 (TLR7) agonist imiquimod mounts strong CTL responses by activation and maturation of skin-derived dendritic cells (DCs) and their migration to lymph nodes. However, TCI based on the commercial formulation Aldara only induces transient CTL responses that needs further improvement for the induction of durable therapeutic immune responses...
June 16, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28642279/role-of-myd88-signaling-in-the-imiquimod-induced-mouse-model-of-psoriasis-focus-on-innate-myeloid-cells
#7
Sara Costa, Olivia Marini, Dalila Bevilacqua, Anthony L DeFranco, Baidong Hou, Silvia Lonardi, William Vermi, Pamela Rodegher, Anna Panato, Franco Tagliaro, Clifford A Lowell, Marco A Cassatella, Giampiero Girolomoni, Patrizia Scapini
Psoriasis is a chronic skin disease associated with deregulated activation of immune cells and keratinocytes. In this study, we used the imiquimod (IMQ)-induced mouse model of psoriasis to dissect better the contribution of hematopoietic and skin-resident stromal cells to psoriasis development. The comparison of disease development in mice carrying the hematopoietic cell-specific deletion of MyD88 (Myd88(fl/fl)Vav-cre(+) mice) with mice carrying the total MyD88 deficiency (Myd88(-/-) mice), we show that the progression of skin and systemic inflammation, as well as of epidermal thickening, was completely dependent on MyD88 expression in hematopoietic cells...
June 22, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28611775/inhibition-of-myeloid-differentiation-factor-88-reduces-human-and-mouse-t-cell-interleukin-17-and-ifn%C3%AE-production-and-ameliorates-experimental-autoimmune-encephalomyelitis-induced-in-mice
#8
Shira Dishon, Shmuel J Cohen, Irun R Cohen, Gabriel Nussbaum
Myeloid differentiation factor 88 (MyD88) recruits signaling proteins to the intracellular domain of receptors belonging to the toll-like/interleukin-1 (IL-1) receptor superfamily. Mice lacking MyD88 are highly susceptible to infectious diseases, but tend to resist experimentally induced autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE) and manifest diminished allograft rejection. We reasoned that inhibition of MyD88 should influence the cytokine profile of responding T cells by blocking costimulatory molecule expression by antigen-presenting cells (APCs) and by inhibiting T-cell responses to IL-18...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28599094/rational-design-of-peptide-derivatives-for-inhibition-of-myd88-mediated-tlr-signaling-in-human-pbmcs-and-epithelial-cells-exposed-to-f-tularensis
#9
D A Ryan, M Degardin, S Alam, T L Kissner, M Hale, M D Cameron, M Rebek, D Ajami, K U Saikh, J Rebek
Small molecules were developed to attenuate proinflammatory cytokines resulting from activation of MyD88-mediated TLR signaling by F. tularensis. Fifty-three tripeptide derivatives were synthesized to mimic a key BB-loop region involved in toll-like/interleukin-1 receptor recognition (TIR) domain interactions. Compounds were tested for inhibition of TNF-α, IFN-γ, IL-6, and IL-1β in human peripheral blood mononuclear cells (PBMCs) and primary human bronchial epithelial cells exposed to LPS extracts from F...
June 9, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28550425/cpg-oligonucleotide-mediated-co-stimulation-of-mouse-invariant-natural-killer-t-cells-negatively-regulates-their-activation-status
#10
Raveendra R Kulkarni, Alexander Ian Villanueva, Leah R Read, Jennifer T Brisbin, Siddhartha Kumar Bhaumik, Jonathan LaMarre, Kaja Murali-Krishna, Shayan Sharif
Invariant natural killer T (iNKT) cells play important roles in antimicrobial defense and immune-regulation. We have previously shown that iNKT cells express certain toll-like receptors (TLR), and that TLR co-stimulation of iNKT cells in the presence of suboptimal concentrations of T cell receptor (TCR) agonists enhances cellular activation. In the present study, we investigated the regulatory effects of CpG oligonucleotides in mouse primary hepatic and splenic iNKT cells and in DN32.D3 iNKT cells. We show that CpG treatment of iNKT cells in the presence of higher concentrations of TCR agonists (α-GalCer or anti-CD3 mAb) results in the up-regulation of TLR9 in iNKT cells with a concurrent reduction in their cellular activation, as assessed by their production of IL-2, IL-4 and IFN-γ compared with controls...
May 27, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28534936/forsythoside-a-exerts-an-anti-endotoxin-effect-by-blocking-the-lps-tlr4-signaling-pathway-and-inhibiting-tregs-in-vitro
#11
Xiao-Yan Zeng, Wei Yuan, Lin Zhou, Shi-Xiu Wang, Yong Xie, Ying-Jun Fu
Endotoxins, also referred to as lipopolysaccharides (LPS), are powerful immunostimulators involved in a number of severe diseases. Forsythoside A (FTA), a monomer of phenethyl alcohol glycosides extracted from Forsythia suspensa, has been shown to possess anti-bacterial and immunomodulatory properties. However, it is currently not known whether FTA can counter the adverse effects of endotoxins. We investigated the effect of FTA on LPS-stimulated RAW264.7 cells and primary lymphocytes to determine its molecular mechanism of action...
May 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28533926/concomitant-lymphoplasmacytic-lymphoma-and-plasma-cell-myeloma-a-diagnostic-challenge
#12
Ahmad T Mansour, Alaleh Esmaeili Shandiz, Michelle K Zimmerman, Trenton D Roth, Jiehao Zhou
BACKGROUND: Lymphoplasmacytic lymphoma and plasma cell myeloma are two B cell lymphoproliferative neoplasms derived from mature B-lymphocytes in different differentiation stages. The coexistence of these two tumors in the same patient is exceedingly rare and can be difficult to diagnose. CASE PRESENTATION: A 76-year-old male presented with a pathologic fracture after a fall. Radiography showed a lytic lesion in the pelvis. Serum immunofixation showed distinct IgM kappa and IgA kappa monoclonal protein bands...
2017: American Journal of Blood Research
https://www.readbyqxmd.com/read/28520792/myd88-signaling-in-dendritic-cells-and-the-intestinal-epithelium-controls-immunity-against-intestinal-infection-with-c-rodentium
#13
Christin Friedrich, Panagiota Mamareli, Sophie Thiemann, Friederike Kruse, Zuobai Wang, Bernhard Holzmann, Till Strowig, Tim Sparwasser, Matthias Lochner
MyD88-mediated signaling downstream of Toll-like receptors and the IL-1 receptor family is critically involved in the induction of protective host responses upon infections. Although it is known that MyD88-deficient mice are highly susceptible to a wide range of bacterial infections, the cell type-specific contribution of MyD88 in protecting the host against intestinal bacterial infection is only poorly understood. In order to investigate the importance of MyD88 in specific immune and nonimmune cell types during intestinal infection, we employed a novel murine knock-in model for MyD88 that enables the cell type-specific reactivation of functional MyD88 expression in otherwise MyD88-deficient mice...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28502093/the-tlr4-trif-pathway-can-protect-against-the-development-of-experimental-allergic-asthma
#14
Karim H Shalaby, Saba Al-Heialy, Kimitake Tsuchiya, Soroor Farahnak, Toby K McGovern, Paul-Andre Risse, Woong-Kyung Suh, Salman T Qureshi, James G Martin
The Toll-like Receptor (TLR) adaptor proteins Myeloid Differentiating Factor 88 (MyD88) and Toll, interleukin-1 Receptor and Resistance protein (TIR) domain-containing adaptor inducing interferon-β (TRIF) comprise the two principal limbs of the TLR signaling network. We studied the role of these adaptors in the TLR4-dependent inhibition of allergic airway disease and induction of CD4+ICOS+ T cells by nasal application of Protollin(™) , a mucosal adjuvant composed of TLR2 and 4 agonists. Wild-type (wt), Trif -/- or Myd88 -/- mice were sensitized to birch pollen extract (BPEx), then received intranasal Protollin followed by consecutive BPEx challenges...
May 14, 2017: Immunology
https://www.readbyqxmd.com/read/28484466/the-st2-il-33-axis-in-immune-cells-during-inflammatory-diseases
#15
REVIEW
Brad Griesenauer, Sophie Paczesny
Il1rl1 (also known as ST2) is a member of the IL-1 superfamily, and its only known ligand is IL-33. ST2 exists in two forms as splice variants: a soluble form (sST2), which acts as a decoy receptor, sequesters free IL-33, and does not signal, and a membrane-bound form (ST2), which activates the MyD88/NF-κB signaling pathway to enhance mast cell, Th2, regulatory T cell (Treg), and innate lymphoid cell type 2 functions. sST2 levels are increased in patients with active inflammatory bowel disease, acute cardiac and small bowel transplant allograft rejection, colon and gastric cancers, gut mucosal damage during viral infection, pulmonary disease, heart disease, and graft-versus-host disease...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28482922/therapeutic-effect-of-schistosoma-japonicum-cystatin-on-bacterial-sepsis-in-mice
#16
Huihui Li, Shushu Wang, Bin Zhan, Wenxin He, Liang Chu, Dapeng Qiu, Nan Li, Yongkun Wan, Hui Zhang, Xingzhi Chen, Qiang Fang, Jilong Shen, Xiaodi Yang
BACKGROUND: Sepsis is a life-threatening complication of an infection and remains one of the leading causes of mortality in surgical patients. Bacteremia induces excessive inflammatory responses that result in multiple organ damage. Chronic helminth infection and helminth-derived materials have been found to immunomodulate host immune system to reduce inflammation against some allergic or inflammatory diseases. Schistosoma japonicum cystatin (Sj-Cys) is a cysteine protease inhibitor that induces regulatory T-cells and a potential immunomodulatory...
May 8, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28468798/plasmacytoid-and-conventional-dendritic-cells-cooperate-in-crosspriming-aav-capsid-specific-cd8-t-cells
#17
Geoffrey L Rogers, Jamie L Shirley, Irene Zolotukhin, Sandeep R P Kumar, Alexandra Sherman, George Q Perrin, Brad E Hoffman, Arun Srivastava, Etiena Basner-Tschakarjan, Mark A Wallet, Cox Terhorst, Moanaro Biswas, Roland W Herzog
Adeno-associated virus (AAV) is a replication-deficient parvovirus that is extensively used as a gene therapy vector. CD8(+) T-cell responses against the AAV capsid protein can, however, affect therapeutic efficacy. Little is known about the in vivo mechanism that leads to the crosspriming of CD8(+) T cells against the input viral capsid antigen. In this study, we report that the Toll-like receptor 9 (TLR9)-MyD88 pattern-recognition receptor pathway is uniquely capable of initiating this response. By contrast, the absence of TLR2, STING, or the addition of TLR4 agonist has no effect...
June 15, 2017: Blood
https://www.readbyqxmd.com/read/28456012/neuregulin-1-positively-modulates-glial-response-and-improves-neurological-recovery-following-traumatic-spinal-cord-injury
#18
Arsalan Alizadeh, Scott M Dyck, Hardeep Kataria, Ghazaleh M Shahriary, Dung H Nguyen, Kallivalappil T Santhosh, Soheila Karimi-Abdolrezaee
Spinal cord injury (SCI) results in glial activation and neuroinflammation, which play pivotal roles in the secondary injury mechanisms with both pro- and antiregeneration effects. Presently, little is known about the endogenous molecular mechanisms that regulate glial functions in the injured spinal cord. We previously reported that the expression of neuregulin-1 (Nrg-1) is acutely and chronically declined following traumatic SCI. Here, we investigated the potential ramifications of Nrg-1 dysregulation on glial and immune cell reactivity following SCI...
April 29, 2017: Glia
https://www.readbyqxmd.com/read/28443609/the-hiv-1-viral-synapse-signals-human-foreskin-keratinocytes-to-secrete-thymic-stromal-lymphopoietin-facilitating-hiv-1-foreskin-entry
#19
Z Zhou, L Xu, A Sennepin, C Federici, Y Ganor, D Tudor, D Damotte, N Barry Delongchamps, M Zerbib, M Bomsel
The complexity of signal transduction resulting from the contact of human immunodeficiency virus type 1 (HIV-1)-infected cells and mucosal cells has hampered our comprehension of HIV-1 mucosal entry. Such process is driven efficiently only by viral synapse contacts, whereas cell-free HIV-1 remains poorly infectious. Using CD4(+) T-cells expressing only HIV-1 envelope inoculated on human adult foreskin tissues, we designed methodologies to identify the signals transduced in foreskin keratinocytes following HIV-1-envelope-dependent viral synapse formation...
April 26, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28418004/host-determinants-of-expression-of-the-helicobacter-pylori-baba-adhesin
#20
Mary E Kable, Lori M Hansen, Cathy M Styer, Samuel L Deck, Olena Rakhimova, Anna Shevtsova, Kathryn A Eaton, Miriam E Martin, Pär Gideonsson, Thomas Borén, Jay V Solnick
Expression of the Helicobacter pylori blood group antigen binding adhesin A (BabA) is more common in strains isolated from patients with peptic ulcer disease or gastric cancer, rather than asymptomatic colonization. Here we used mouse models to examine host determinants that affect H. pylori BabA expression. BabA expression was lost by phase variation as frequently in WT mice as in RAG2-/- mice that do not have functional B or T cells, and in MyD88-/-, TLR2-/- and TLR4-/- mice that are defective in toll like receptor signaling...
April 18, 2017: Scientific Reports
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