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MyD88 in T cells

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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-cross-priming-aav-capsid-specific-cd8-t-cells
#7
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 cross-priming of CD8(+) T cells against the input viral capsid antigen. Here we report that the TLR9-MyD88 pattern-recognition receptor pathway is uniquely capable of initiating this response. By contrast, the absence of TLR2, STING, or addition of TLR4 agonist has no effect...
May 3, 2017: Blood
https://www.readbyqxmd.com/read/28456012/neuregulin-1-positively-modulates-glial-response-and-improves-neurological-recovery-following-traumatic-spinal-cord-injury
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28405493/hla-class-i-restricted-myd88-l265p-derived-peptides-as-specific-targets-for-lymphoma-immunotherapy
#11
Annika Nelde, Juliane Sarah Walz, Daniel Johannes Kowalewski, Heiko Schuster, Olaf-Oliver Wolz, Janet Kerstin Peper, Yamel Cardona Gloria, Anton W Langerak, Alice F Muggen, Rainer Claus, Irina Bonzheim, Falko Fend, Helmut Rainer Salih, Lothar Kanz, Hans-Georg Rammensee, Stefan Stevanović, Alexander N R Weber
Genome sequencing has uncovered an array of recurring somatic mutations in different non-Hodgkin lymphoma (NHL) subtypes. If affecting protein-coding regions, such mutations may yield mutation-derived peptides that may be presented by HLA class I proteins and recognized by cytotoxic T cells. A recurring somatic and oncogenic driver mutation of the Toll-like receptor adaptor protein MYD88, Leu265Pro (L265P) was identified in up to 90% of different NHL subtype patients. We therefore screened the potential of MYD88(L265P)-derived peptides to elicit cytotoxic T cell responses as tumor-specific neoantigens...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28404732/roles-of-the-traf6-and-pellino-e3-ligases-in-myd88-and-rankl-signaling
#12
Sam Strickson, Christoph H Emmerich, Eddy T H Goh, Jiazhen Zhang, Ian R Kelsall, Thomas Macartney, C James Hastie, Axel Knebel, Mark Peggie, Francesco Marchesi, J Simon C Arthur, Philip Cohen
It is widely accepted that the essential role of TRAF6 in vivo is to generate the Lys63-linked ubiquitin (K63-Ub) chains needed to activate the "master" protein kinase TAK1. Here, we report that TRAF6 E3 ligase activity contributes to but is not essential for the IL-1-dependent formation of K63-Ub chains, TAK1 activation, or IL-8 production in human cells, because Pellino1 and Pellino2 generate the K63-Ub chains required for signaling in cells expressing E3 ligase-inactive TRAF6 mutants. The IL-1-induced formation of K63-Ub chains and ubiquitylation of IRAK1, IRAK4, and MyD88 was abolished in TRAF6/Pellino1/Pellino2 triple-knockout (KO) cells, but not in TRAF6 KO or Pellino1/2 double-KO cells...
April 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28402840/high-molecular-weight-components-containing-n-linked-oligosaccharides-of-ascaris-suum-extract-inhibit-the-dendritic-cells-activation-through-dc-sign-and-mr
#13
Bruna C Favoretto, Adriana A C Casabuono, José A Portes-Junior, Jacqueline F Jacysyn, Alicia S Couto, Eliana L Faquim-Mauro
Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. High molecular weight components (PI) from Ascaris suum extract down-modulate the immune response against ovalbumin (OVA). The PI exerts direct effect on dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule and, thus, decreases the T lymphocytes response. Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity...
April 9, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28393847/knockdown-of-toll-like-receptor-4-signaling-pathways-ameliorate-bone-graft-rejection-in-a-mouse-model-of-allograft-transplantation
#14
Jeng-Long Hsieh, Po-Chuan Shen, Po-Ting Wu, I-Ming Jou, Chao-Liang Wu, Ai-Li Shiau, Chrong-Reen Wang, Hao-Earn Chong, Shu-Han Chuang, Jia-Shiou Peng, Shih-Yao Chen
Non-union occurring in structural bone grafting is a major problem in allograft transplantation because of impaired interaction between the host and graft tissue. Activated toll-like receptor (TLR) induces inflammatory cytokines and chemokines and triggers cell-mediated immune responses. The TLR-mediated signal pathway is important for mediating allograft rejection. We evaluated the effects of local knockdown of the TLR4 signaling pathway in a mouse segmental femoral graft model. Allografts were coated with freeze-dried lentiviral vectors that encoded TLR4 and myeloid differentiation primary response gene 88 (MyD88) short-hairpin RNA (shRNA), which were individually transplanted into the mice...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28356067/probiotic-bacteria-prevent-salmonella-induced-suppression-of-lymphoproliferation-in-mice-by-an-immunomodulatory-mechanism
#15
R Doug Wagner, Shemedia J Johnson
BACKGROUND: Salmonella enterica infections often exhibit a form of immune evasion. We previously observed that probiotic bacteria could prevent inhibition of lymphoproliferation and apoptosis responses of T cells associated with S. enterica infections in orally challenged mice. RESULTS: In this study, changes in expression of genes related to lymphocyte activation in mucosa-associated lymphoid tissues (MALT) of mice orally infected with S. enterica with and without treatment with probiotic bacteria were evaluated...
March 29, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28339054/overexpression-of-tim-3-reduces-helicobacter-pylori-associated-inflammation-through-tlr4-nf%C3%AE%C2%BAb-signaling-in%C3%A2-vitro
#16
Fucai Wang, Zhirong Mao, Dongsheng Liu, Jing Yu, Youhua Wang, Wen Ye, Dongjia Lin, Nanjin Zhou, Yong Xie
The present study aimed to investigate the interaction between T-cell immunoglobulin and mucin-domain-containing molecule-3 (Tim-3) and Toll-like receptor 4 (TLR4)/nuclear factor κB (NF‑κB) signaling in Helicobacter pylori-infected RAW264.7 macrophage cells. RAW264.7 cells were co‑cultured with H. pylori SS1 at different bacteria/cell ratios, and subsequently the mRNA expression of Tim‑3, TLR4, and myeloid differentiation factor 88 (MyD88) was measured by reverse transcription-quantitative polymerase chain reaction (RT‑qPCR)...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28262817/om-85-is-an-immunomodulator-of-interferon-%C3%AE-production-and-inflammasome-activity
#17
A T Dang, C Pasquali, K Ludigs, G Guarda
The inflammasome-IL-1 axis and type I interferons (IFNs) have been shown to exert protective effects upon respiratory tract infections. Conversely, IL-1 has also been implicated in inflammatory airway pathologies such as asthma and chronic obstructive pulmonary disease (COPD). OM-85 is a bacterial extract with proved efficacy against COPD and recurrent respiratory tract infections, a cause of co-morbidity in asthmatic patients. We therefore asked whether OM-85 affects the above-mentioned innate immune pathways...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28259699/chicken-il-26-regulates-immune-responses-through-the-jak-stat-and-nf-%C3%AE%C2%BAb-signaling-pathways
#18
Anh Duc Truong, Yeojin Hong, Cong Thanh Hoang, Janggeun Lee, Yeong Ho Hong
Chicken interleukin 26 (ChIL-26), a member of the IL-10 family, is expressed in T cells and can induce expression of proinflammatory cytokines. We examined the response of signal transduction pathways to ChIL-26 stimulation in the chicken T (CU91), macrophage (HD11), and fibroblast (OU2) cell lines. ChIL-26 activated JAK2 and TYK2 phosphorylation, as well as activation of STAT1, STAT3, and SHP2 via tyrosine/serine residues. We also showed that ChIL-26 activates the phosphorylation of NF-κB1, TAK1, and MyD88 kinase, which are key regulators of NF-κB signaling pathways...
March 2, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28235842/acquired-mutations-associated-with-ibrutinib-resistance-in-waldenstr%C3%A3-m-macroglobulinemia
#19
Lian Xu, Nicholas Tsakmaklis, Guang Yang, Jiaji G Chen, Xia Liu, Maria Demos, Amanda Kofides, Christopher J Patterson, Kirsten Meid, Joshua Gustine, Toni Dubeau, M Lia Palomba, Ranjana Advani, Jorge J Castillo, Richard R Furman, Zachary R Hunter, Steven P Treon
Ibrutinib produces high response rates and durable remissions in Waldenström macroglobulinemia (WM) that are impacted by MYD88 and CXCR4(WHIM) mutations. Disease progression can develop on ibrutinib, although the molecular basis remains to be clarified. We sequenced sorted CD19(+) lymphoplasmacytic cells from 6 WM patients who progressed after achieving major responses on ibrutinib using Sanger, TA cloning and sequencing, and highly sensitive and allele-specific polymerase chain reaction (AS-PCR) assays that we developed for Bruton tyrosine kinase (BTK) mutations...
May 4, 2017: Blood
https://www.readbyqxmd.com/read/28220116/cpg-odn-shapes-alum-adjuvant-activity-signaling-via-myd88-and-il-10
#20
Luciana Mirotti, Ricardo Wesley Alberca Custódio, Eliane Gomes, Florencia Rammauro, Eliseu Frank de Araujo, Vera Lucia Garcia Calich, Momtchilo Russo
Aluminum-containing adjuvants usually referred as Alum are considered as T helper type-2 (Th2) adjuvants, while agonists of toll-like receptors (TLRs) are viewed as adjuvants that favor Th1/Th17 immunity. Alum has been used in numerous vaccine formulations; however, its undesired pro-Th2 adjuvant activity constitutes a caveat for Alum-based vaccines. Combining Alum with TLR-dependent, pro-Th1/Th17 adjuvants might dampen the pro-Th2 activity and improve the effectiveness of vaccine formulations. Here, using the ovalbumin (OVA) model of allergic lung inflammation, we found that sensitization with the synthetic TLR9 agonist, which is composed of oligodeoxynucleotides containing CpG motifs adsorbed to Alum, inhibited the development of OVA-induced lung allergic Th2 responses without shifting toward a Th1 pattern...
2017: Frontiers in Immunology
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