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MyD88 in T cells

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https://www.readbyqxmd.com/read/27888719/treponema-pallidum-flagellin-flaa2-induces-il-6-secretion-in-thp-1-cells-via-the-toll-like-receptor-2-signaling-pathway
#1
Yafeng Xie, Man Xu, Yongjian Xiao, Zhuoran Liu, Chuanhao Jiang, Xingxing Kuang, Chuan Wang, Haiying Wu, Jing Peng, Chun Li, Yu Wang, Huaming Liu, Bin Liu, Xiaotuan Zhang, Feijun Zhao, Tiebing Zeng, Shuangquan Liu, Yimou Wu
Treponema pallidum subsp. pallidum membrane proteins are considered as potent inducers in the initiation and development of inflammation. In the present study, the mechanism that leads to the production of interleukin 6 (IL-6), one of the key proinflammatory cytokines, by human monocytic THP-1 cells when these cells are treated with T. pallidum flagellin FlaA2 was investigated. Stimulation with flagellin FlaA2 can induce IL-6 expression in human monocytes and augment the phosphorylation of ERK, p38, and NF-κB, but has no effect on the phosphorylation of JNK...
November 23, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27872207/myeloid-specific-gene-deletion-of-protein-phosphatase-2a-magnifies-myd88-and-trif-dependent-inflammation-following-endotoxin-challenge
#2
Lei Sun, Tiffany T Pham, Timothy T Cornell, Kelli L McDonough, Walker M McHugh, Neal B Blatt, Mary K Dahmer, Thomas P Shanley
Protein phosphatase 2A (PP2A) is a member of the intracellular serine/threonine phosphatases. Innate immune cell activation triggered by pathogen-associated molecular patterns is mediated by various protein kinases, and PP2A plays a counter-regulatory role by deactivating these kinases. In this study, we generated a conditional knockout of the α isoform of the catalytic subunit of PP2A (PP2ACα). After crossing with myeloid-specific cre-expressing mice, effective gene knockout was achieved in various myeloid cells...
November 21, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27864347/human-pancreatic-cancer-cells-induce-a-myd88-dependent-stromal-response-to-promote-a-tumor-tolerant-immune-microenvironment
#3
Daniel Delitto, Andrea E Delitto, Bayli B DiVita, Kien Pham, Song Han, Emily R Hartlage, Brittney N Newby, Michael H Gerber, Kevin E Behrns, Lyle L Moldawer, Ryan M Thomas, Thomas George, Todd Brusko, Clayton E Mathews, Chen Liu, Jose G Trevino, Steven J Hughes, Shannon Wallet
Cancer cells exert mastery over the local tumor-associated stroma (TAS) to configure protective immunity within the tumor microenvironment. The immunomodulatory character of pancreatic lysates of patients with cancer differs from those with pancreatitis. In this study, we evaluated the crosstalk between pancreatic cancer (PC) and its TAS in primary human cell culture models. Upon exposure of TAS to PC cell-conditioned media, we documented robust secretion of IL-6 and IL-8. This TAS response was MyD88-dependent and sufficient to directly suppress both CD4+ and CD8+ T cell proliferation, inducing Th17 polarization at the expense of Th1...
November 18, 2016: Cancer Research
https://www.readbyqxmd.com/read/27856326/expression-pattern-analysis-of-irf4-and-its-related-genes-revealed-the-functional-differentiation-of-irf4-paralogues-in-teleost
#4
Kete Ai, Kai Luo, Youshen Li, Wei Hu, Weihua Gao, Liu Fang, Guangming Tian, Guoliang Ruan, Qiaoqing Xu
In mammals, interferon regulatory factor 4 (IRF4) plays an important role in the process of development and differentiation of B cells, T cells and dendritic cells. It can regulate immune pathway through IRF5, MyD88, IL21, PGC1α, and NOD2. In the present study, we investigated the expression pattern of IRF4 paralogues and these related genes for the first time in teleosts. The results showed that these genes were all expressed predominantly in known immune tissues while IRF5 was also relatively highly expressed in muscle...
November 14, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27836955/ifn-%C3%AE-ifn-%C3%AE-responses-to-respiratory-viruses-in-paediatric-asthma
#5
Annika Bergauer, Nina Sopel, Bettina Kroß, Tytti Vuorinen, Paraskevi Xepapadaki, Scott T Weiss, Ashley Blau, Himanshu Sharma, Cornelia Kraus, Rebekka Springel, Manfred Rauh, Susanne Mittler, Anna Graser, Theodor Zimmermann, Volker O Melichar, Alexander Kiefer, Marek L Kowalski, Anna Sobanska, Tuomas Jartti, Heikki Lukkarinen, Nikolaos G Papadopoulos, Susetta Finotto
We analysed the influence of rhinovirus (RV) in nasopharyngeal fluid (NPF) on type I and III interferon (IFN) responses (e.g. IFN-α and IFN -: λ) and their signal transduction, at baseline and during disease exacerbation, in cohorts of pre-school children with and without asthma.At the time of recruitment into the Europe-wide study PreDicta, and during symptoms, NPF was collected and the local RV colonisation was analysed. Peripheral blood mononuclear cells (PBMCs) were challenged in vitro with RV or not...
November 11, 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/27825468/novel-therapeutic-targets-in-waldenstrom-macroglobulinemia
#6
REVIEW
Aneel Paulus, Sikander Ailawadhi, Asher Chanan-Khan
Understanding of molecular mechanisms that drive Waldenstrom macroglobulinemia (WM) cell survival are rapidly evolving. This review briefly highlights emerging "WM-relevant" targets; for which therapeutic strategies are currently being investigated in preclinical and clinical studies. With the discovery of MYD88L265P signaling and remarkable activity of ibrutinib in WM, other targets within the B-cell receptor pathway are now being focused on for therapeutic intervention. Additional targets which play a role in WM cell survival include TLR7, 8 and 9, proteasome-associated deubiquitinating enzymes (USP14 and UCHL5), XPO1/CRM1 and AURKA...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27813535/coinhibition-of-the-deubiquitinating-enzymes-usp14-and-uchl5-with-vlx1570-is-lethal-to-ibrutinib-or-bortezomib-resistant-waldenstrom-macroglobulinemia-tumor-cells
#7
A Paulus, S Akhtar, T R Caulfield, K Samuel, H Yousaf, Y Bashir, S M Paulus, D Tran, R Hudec, D Cogen, J Jiang, B Edenfield, A Novak, S M Ansell, T Witzig, P Martin, M Coleman, V Roy, S Ailawadhi, K Chitta, S Linder, A Chanan-Khan
The survival of Waldenstrom macroglobulinemia (WM) tumor cells hinges on aberrant B-cell receptor (BCR) and MYD88 signaling. WM cells upregulate the proteasome function to sustain the BCR-driven growth while maintaining homeostasis. Clinically, two treatment strategies are used to disrupt these complementary yet mutually exclusive WM survival pathways via ibrutinib (targets BTK/MYD88 node) and bortezomib (targets 20 S proteasome). Despite the success of both agents, WM patients eventually become refractory to treatment, highlighting the adaptive plasticity of WM cells and underscoring the need for development of new therapeutics...
November 4, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27798617/fibroblastic-reticular-cells-regulate-intestinal-inflammation-via-il-15-mediated-control-of-group-1-ilcs
#8
Cristina Gil-Cruz, Christian Perez-Shibayama, Lucas Onder, Qian Chai, Jovana Cupovic, Hung-Wei Cheng, Mario Novkovic, Philipp A Lang, Markus B Geuking, Kathy D McCoy, Shinya Abe, Guangwei Cui, Koichi Ikuta, Elke Scandella, Burkhard Ludewig
Fibroblastic reticular cells (FRCs) of secondary lymphoid organs form distinct niches for interaction with hematopoietic cells. We found here that production of the cytokine IL-15 by FRCs was essential for the maintenance of group 1 innate lymphoid cells (ILCs) in Peyer's patches and mesenteric lymph nodes. Moreover, FRC-specific ablation of the innate immunological sensing adaptor MyD88 unleashed IL-15 production by FRCs during infection with an enteropathogenic virus, which led to hyperactivation of group 1 ILCs and substantially altered the differentiation of helper T cells...
December 2016: Nature Immunology
https://www.readbyqxmd.com/read/27798160/water-in-oil-only-adjuvants-selectively-promote-t-follicular-helper-cell-polarization-through-a-type-i-ifn-and-il-6-dependent-pathway
#9
Nicolas Riteau, Andrea J Radtke, Kevin Shenderov, Lara Mittereder, Sandra D Oland, Sara Hieny, Dragana Jankovic, Alan Sher
T follicular helper (Tfh) cells are a subset of CD4(+) T lymphocytes that promote the development of humoral immunity. Although the triggers required for the differentiation of the other major Th subsets are well defined, those responsible for Tfh cell responses are still poorly understood. We determined that mice immunized with peptide or protein Ags emulsified in IFA or related water-in-oil adjuvants develop a highly polarized response in which the majority of the Ag-specific CD4(+) T cells are germinal center-homing CXCR5(+)Bcl6(+) Tfh cells...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27796360/pollen-tlr4-innate-immunity-signaling-initiates-il-33-st2-th2-pathways-in-allergic-inflammation
#10
Jin Li, Lili Zhang, Xin Chen, Ding Chen, Xia Hua, Fang Bian, Ruzhi Deng, Fan Lu, Zhijie Li, Stephen C Pflugfelder, De-Quan Li
Innate immunity has been extended to respond environmental pathogen other than microbial components. Here we explore a novel pollen/TLR4 innate immunity in allergic inflammation. In experimental allergic conjunctivitis induced by short ragweed (SRW) pollen, typical allergic signs, stimulated IL-33/ST2 signaling and overproduced Th2 cytokine were observed in ocular surface, cervical lymph nodes and isolated CD4(+) T cells of BALB/c mice. These clinical, cellular and molecular changes were significantly reduced/eliminated in TLR4 deficient (Tlr4-d) or MyD88 knockout (MyD88(-/-)) mice...
October 31, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27795867/the-role-of-tlr2-tlr4-and-tlr9-in-the-pathogenesis-of-atherosclerosis
#11
REVIEW
Mohsin H K Roshan, Amos Tambo, Nikolai P Pace
Toll-like receptors (TLRs) are key players in the pathogenesis of inflammatory conditions including coronary arterial disease (CAD). They are expressed by a variety of immune cells where they recognize pathogen-associated molecular patterns (PAMPs). TLRs recruit adaptor molecules, including myeloid differentiation primary response protein (MYD88) and TIRF-related adaptor protein (TRAM), to mediate activation of MAPKs and NF-kappa B pathways. They are associated with the development of CAD through various mechanisms...
2016: International Journal of Inflammation
https://www.readbyqxmd.com/read/27783947/inflammatory-th1-and-th17-in-the-intestine-are-each-driven-by-functionally-specialized-dendritic-cells-with-distinct-requirements-for-myd88
#12
Jie Liang, Hsin-I Huang, Fernanda P Benzatti, Amelia B Karlsson, Junyi J Zhang, Nourhan Youssef, Averil Ma, Laura P Hale, Gianna E Hammer
Normal dynamics between microbiota and dendritic cells (DCs) support modest numbers of T cells, yet these do not cause inflammation. The DCs that induce inflammatory T cells and the signals that drive this process remain unclear. Here, we demonstrate that small intestine DCs lacking the signaling attenuator A20 induce inflammatory T cells and that the signals perceived and antigen-presenting cell (APC) functions are unique for different DC subsets. Thus, although CD103(+)CD11b(-) DCs exclusively instruct IFNγ(+) T cells, CD103(+)CD11b(+) DCs exclusively instruct IL-17(+) T cells...
October 25, 2016: Cell Reports
https://www.readbyqxmd.com/read/27741278/myd88-cd40-genetic-adjuvant-function-in-cutaneous-atypical-antigen-presenting-cells-contributes-to-dna-vaccine-immunogenicity
#13
Matthew R Collinson-Pautz, Kevin M Slawin, Jonathan M Levitt, David M Spencer
Therapeutic DNA-based vaccines aim to prime an adaptive host immune response against tumor-associated antigens, eliminating cancer cells primarily through CD8+ cytotoxic T cell-mediated destruction. To be optimally effective, immunological adjuvants are required for the activation of tumor-specific CD8+ T cells responses by DNA vaccination. Here, we describe enhanced anti-tumor efficacy of an in vivo electroporation-delivered DNA vaccine by inclusion of a genetically encoded chimeric MyD88/CD40 (MC) adjuvant, which integrates both innate and adaptive immune signaling pathways...
2016: PloS One
https://www.readbyqxmd.com/read/27721403/cxcl2-mif-cxcr2-signaling-promotes-the-recruitment-of-myeloid-derived-suppressor-cells-and-is-correlated-with-prognosis-in-bladder-cancer
#14
H Zhang, Y-L Ye, M-X Li, S-B Ye, W-R Huang, T-T Cai, J He, J-Y Peng, T-H Duan, J Cui, X-S Zhang, F-J Zhou, R-F Wang, J Li
The accumulation of myeloid-derived suppressor cells (MDSCs) has been observed in solid tumors and is correlated with tumor progression; however, the underlying mechanism is still poorly understood. In this study, we identified a mechanism by which tumor cells induce MDSC accumulation and expansion in the bladder cancer (BC) microenvironment via CXCL2/MIF-CXCR2 signaling. Elevated expression of CXCL2 and MIF and an increased number of CD33(+) MDSCs were detected in BC tissues, and these increases were significantly associated with advanced disease stage and poor patient prognosis (P<0...
October 10, 2016: Oncogene
https://www.readbyqxmd.com/read/27693915/tlr9-played-a-more-important-role-than-tlr2-in-the-combination-of-maltose-binding-protein-and-bcg-induced-th1-activation
#15
Weihua Ni, Fang Wang, Guomu Liu, Nannan Zhang, Hongyan Yuan, Jing Jie, Guixiang Tai
Our previous study demonstrated that maltose-binding protein (MBP) combined with BCG induced synergistic mouse Th1 activation in vivo. Here, to explore the mechanism of MBP combined with BCG on Th1 activation, mouse purified CD4(+) T cells were stimulated with MBP and BCG in vitro. The results showed that MBP combined with BCG synergistically increased IFN-γ production, accompanied with the upregulation of TLR2/9 expressions, suggesting that TLR2/9 were involved in the combination-induced Th1 activation. Next, TLR2 antibodies and TLR9 inhibitor were used to further analyze the effects of TLRs in Th1 activation...
September 28, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27687589/immune-adjuvant-effect-of-a-toxoplasma-gondii-profilin-like-protein-in-autologous-whole-tumor-cell-vaccination-in-mice
#16
Kyoung-Ho Pyo, You-Won Lee, Sun Min Lim, Eun-Hee Shin
Profilin-like protein in Toxoplasma gondii (TgPLP) is a Toll-like receptor (TLR) agonist. In this study, we investigated whether TgPLP has an adjuvant effect on immune function in autologous whole-tumor-cell vaccine (AWV) treatment. Mice vaccinated with AWV together with recombinant TgPLP protein had smaller CT26 tumors and increased survival. TgPLP treatment strongly increased the production of IL-12 through MyD88 signaling and several chemokines, including CCL5, CCL12, and XCL1, in bone marrow-derived macrophages (BMMs)...
September 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27659428/prevention-of-allograft-rejection-in-heart-transplantation-through-concurrent-gene-silencing-of-tlr-and-kinase-signaling-pathways
#17
Hongmei Wang, Xusheng Zhang, Xiufen Zheng, Zhu Lan, Jun Shi, Jifu Jiang, Terry Zwiep, Qing Li, Douglas Quan, Zhu-Xu Zhang, Weiping Min
Toll-like receptors (TLRs) act as initiators and conductors responsible for both innate and adaptive immune responses in organ transplantation. The mammalian target of rapamycin (mTOR) is one of the most critical signaling kinases that affects broad aspects of cellular functions including metabolism, growth, and survival. Recipients (BALB/c) were treated with MyD88, TRIF and mTOR siRNA vectors, 3 and 7 days prior to heart transplantation and 7, 14 and 21 days after transplantation. After siRNA treatment, recipients received a fully MHC-mismatched C57BL/6 heart...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27625307/general-but-not-myeloid-or-type-ii-lung-epithelial-cell-myeloid-differentiation-factor-88-deficiency-abrogates-house-dust-mite-induced-allergic-lung-inflammation
#18
A A Anas, J Yang, J Daan de Boer, J J T H Roelofs, B Hou, A F de Vos, T van der Poll
Asthma is a highly prevalent chronic allergic inflammatory disease of the airways affecting people worldwide. House dust mite (HDM) is the most common allergen implicated in human allergic asthma. HDM-induced allergic responses are thought to depend upon activation of pathways involving Toll-like receptors and their adaptor protein myeloid differentiation factor 88 (MyD88). We sought here to determine the role of MyD88 in myeloid and type II lung epithelial cells in the development of asthma-like allergic disease using a mouse model...
September 14, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27623761/chloroquine-suppresses-the-development-of-hypertension-in-spontaneously-hypertensive-rats
#19
Cameron G McCarthy, Camilla F Wenceslau, Styliani Goulopoulou, Babak Baban, Takayuki Matsumoto, R Clinton Webb
BACKGROUND: Innate immune system responses to damage-associated molecular patterns (DAMPs) are involved in hypertension. However, the mechanisms of this contribution are not well understood. Circulating mitochondrial DNA is a DAMP that activates Toll-like receptor (TLR) 9 and is elevated in spontaneously hypertensive rats (SHR). Therefore, we hypothesized that lysosomotropic agent chloroquine (CQ) would impair TLR9 signaling, as well as prevent the development of hypertension and immune cell recruitment to the vasculature, in SHR...
September 13, 2016: American Journal of Hypertension
https://www.readbyqxmd.com/read/27622036/tumor-released-autophagosomes-induce-il-10-producing-b-cells-with-suppressive-activity-on-t-lymphocytes-via-tlr2-myd88-nf-%C3%AE%C2%BAb-signal-pathway
#20
Meng Zhou, Zhifa Wen, Feng Cheng, Jie Ma, Weixia Li, Hongyan Ren, Yemeng Sheng, Huixia Dong, Liwei Lu, Hong-Ming Hu, Li-Xin Wang
Recent studies have shown that tumor cells can release autophagosomes, which transport a broad array of biologically active molecules with potential modulatory effects on immune cell functions. In this study, we aimed to investigate the role of tumor cells-released autophagosomes (i.e. TRAP) in regulating B cell differentiation and function. TRAPs from murine tumor cell lines were found to induce splenic B cells to differentiate into IL-10-producing regulatory B cells (Bregs) with a distinct phenotype of CD1d(+) CD5(+), which could potently inhibit CD8(+) and CD4(+) T cell responses in IL-10-depedent manner both in vitro and in vivo...
July 2016: Oncoimmunology
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