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https://www.readbyqxmd.com/read/29349889/t-cell-immunoglobulin-and-itim-domain-contributes-to-cd8-t-cell-immunosenescence
#1
Yangzi Song, Beibei Wang, Rui Song, Yu Hao, Di Wang, Yuxin Li, Yu Jiang, Ling Xu, Yaluan Ma, Hong Zheng, Yaxian Kong, Hui Zeng
Aging is associated with immune dysfunction, especially T-cell defects, which result in increased susceptibility to various diseases. Previous studies showed that T cells from aged mice express multiple inhibitory receptors, providing evidence of the relationship between T-cell exhaustion and T-cell senescence. In this study, we showed that T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), a novel co-inhibitory receptor, was upregulated in CD8+ T cells of elderly adults...
January 19, 2018: Aging Cell
https://www.readbyqxmd.com/read/29345376/role-of-negative-regulation-of-immune-signaling-pathways-in-neutrophil-function
#2
REVIEW
Veronica Azcutia, Charles A Parkos, Jennifer C Brazil
Polymorphonuclear neutrophils (PMNs) play a critical role in host defense against infection and in the resolution of inflammation. However, immune responses mediated by PMN must be tightly regulated to facilitate elimination of invading pathogens without inducing detrimental inflammation and host tissue damage. Specific engagement of cell surface immunoreceptors by a diverse range of extracellular signals regulates PMN effector functions through differential activation of intracellular signaling cascades. Although mechanisms of PMN activation mediated via cell signaling pathways have been well described, less is known about negative regulation of PMN function by immune signaling cascades...
December 19, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29301754/maintenance-of-murine-platelet-homeostasis-by-the-kinase-csk-and-the-phosphatase-cd148
#3
Jun Mori, Zoltan Nagy, Giada Di Nunzio, Christopher W Smith, Mitchell J Geer, Rashid Al Ghaithi, Johanna P van Geffen, Silke Heising, Luke Boothman, Bibian M E Tullemans, Joao N Correia, Louise Tee, Marijke J E Kuijpers, Paul Harrison, Johan W M Heemskerk, Gavin E Jarvis, Alexander Tarakhovsky, Arthur Weiss, Alexandra Mazharian, Yotis A Senis
Src family kinases (SFKs) coordinate the initiating and propagating activation signals in platelets, however it remains unclear how they are regulated. Here we show that ablation of C-terminal Src kinase (Csk) and receptor-like protein tyrosine-phosphatase CD148 in mice results in a dramatic increase in platelet SFK activity, demonstrating that these proteins are essential regulators of platelet reactivity. Paradoxically, Csk/CD148-deficient mice exhibit reduced in vivo and ex vivo thrombus formation and increased bleeding following injury, rather than a prothrombotic phenotype...
January 4, 2018: Blood
https://www.readbyqxmd.com/read/29295843/gpvi-signaling-is-compromised-in-newly-formed-young-platelets-after-acute-thrombocytopenia-in-mice
#4
Shuchi Gupta, Deya Cherpokova, Markus Spindler, Martina Morowski, Markus Bender, Bernhard Nieswandt
At sites of vascular injury, exposed subendothelial collagens trigger platelet activation and thrombus formation by interacting with the immunoreceptor tyrosine-based activation motif (ITAM)-coupled glycoprotein (GP) VI on the platelet surface. Platelets are derived from the cytoplasm of megakaryocytes (MKs), which extend large proplatelets into bone marrow (BM) sinusoids that are then released into the blood stream where the final platelet sizing and maturation occurs. The mechanisms that prevent activation of MKs and forming proplatelets in the collagen-rich BM environment remain largely elusive...
January 2, 2018: Blood
https://www.readbyqxmd.com/read/29275861/natural-killer-cells-control-tumor-growth-by-sensing-a-growth-factor
#5
Alexander D Barrow, Melissa A Edeling, Vladimir Trifonov, Jingqin Luo, Piyush Goyal, Benjamin Bohl, Jennifer K Bando, Albert H Kim, John Walker, Mary Andahazy, Mattia Bugatti, Laura Melocchi, William Vermi, Daved H Fremont, Sarah Cox, Marina Cella, Christian Schmedt, Marco Colonna
Many tumors produce platelet-derived growth factor (PDGF)-DD, which promotes cellular proliferation, epithelial-mesenchymal transition, stromal reaction, and angiogenesis through autocrine and paracrine PDGFRβ signaling. By screening a secretome library, we found that the human immunoreceptor NKp44, encoded by NCR2 and expressed on natural killer (NK) cells and innate lymphoid cells, recognizes PDGF-DD. PDGF-DD engagement of NKp44 triggered NK cell secretion of interferon gamma (IFN)-γ and tumor necrosis factor alpha (TNF-α) that induced tumor cell growth arrest...
December 20, 2017: Cell
https://www.readbyqxmd.com/read/29232689/a-computational-model-for-regulation-of-nanoscale-glucan-exposure-in-candida-albicans
#6
Michael J Wester, Jia Lin, Aaron K Neumann
Candida albicans is a virulent human opportunistic pathogen. It evades innate immune surveillance by masking an immunogenic cell wall polysaccharide, β-glucan, from recognition by the immunoreceptor Dectin-1. Glucan unmasking by the antifungal drug caspofungin leads to changes in the nanostructure of glucan exposure accessible to Dectin-1. The physical mechanism that regulates glucan exposure is poorly understood, but it controls the nanobiology of fungal pathogen recognition. We created computational models to simulate hypothetical physical processes of unmasking glucan in a biologically realistic distribution of cell wall glucan fibrils...
2017: PloS One
https://www.readbyqxmd.com/read/29211042/newly-emerging-immune-checkpoints-promises-for-future-cancer-therapy
#7
REVIEW
Robert J Torphy, Richard D Schulick, Yuwen Zhu
Cancer immunotherapy has been a great breakthrough, with immune checkpoint inhibitors leading the way. Despite the clinical effectiveness of certain immune checkpoint inhibitors, the overall response rate remains low, and the effectiveness of immunotherapies for many tumors has been disappointing. There is substantial interest in looking for additional immune checkpoint molecules that may act as therapeutic targets for cancer. Recent advances during the last decade have identified several novel immune checkpoint targets, including lymphocyte activation gene-3 (LAG-3), B and T lymphocyte attenuator (BTLA), programmed death-1 homolog (PD-1H), T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIM-3)/carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), and the poliovirus receptor (PVR)-like receptors...
December 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29208681/hemitam-a-single-tyrosine-motif-that-packs-a-punch
#8
REVIEW
Björn Bauer, Alexander Steinle
Innate immune cells sense danger through a plethora of germline-encoded receptors that recognize pathogen-associated molecular patterns (PAMPs) or cellular molecules that are exposed only by stressed, infected, malignant, or dead cells. Many of these danger-sensing receptors belong to the C-type lectin-like superfamily (CLSF) and therefore are called C-type lectin-like receptors (CTLRs). Certain activating CTLRs, namely, CLEC-2, Dectin-1, DNGR-1, NKp80, and NKp65, which are encoded by genes that are clustered together in a subregion of the mammalian natural killer gene complex (NKC), use a single copy tyrosine signaling module termed the hemi-immunoreceptor tyrosine-based activation motif (hemITAM)...
December 5, 2017: Science Signaling
https://www.readbyqxmd.com/read/29187378/platelet-glycoprotein-vi-aids-in-local-immunity-during-gram-negative-pneumonia-derived-sepsis
#9
Theodora A M Claushuis, Alex F de Vos, Bernhard Nieswandt, Louis Boon, Joris J T H Roelofs, Onno J de Boer, Cornelis J van 't Veer, Tom van der Poll
Platelet collagen receptor glycoprotein(GP)VI and podoplanin receptor C-type lectin-like receptor (CLEC-)2 are receptors implicated in platelet activation that both signal via an immunoreceptor-tyrosine-based activation motif. Platelets are necessary for host defense and prevention of hemorrhage during sepsis, but the role of platelet GPVI and CLEC2 herein is unknown. To investigate this we infected mice depleted of platelet GPVI or CLEC2 by antibody treatment or GPVI-/- mice with the common human sepsis pathogen Klebsiella pneumoniae via the airways to induce pneumonia derived sepsis...
November 29, 2017: Blood
https://www.readbyqxmd.com/read/29163499/fc%C3%AE%C2%B5ri-%C3%AE-chain-negatively-modulates-dectin-1-responses-in-dendritic-cells
#10
Yi-Gen Pan, Yen-Ling Yu, Chi-Chien Lin, Lewis L Lanier, Ching-Liang Chu
The inhibitory effect of immunoreceptor tyrosine-based activation motif (ITAM)-containing adapters DAP12 and FcεRI γ-chain (FcRγ) has been found in many immune functions. Herein, we have further explored the role of these adapters in C-type lectin receptors response. We identified that FcRγ, but not DAP12, could negatively regulate the Dectin-1 responses in dendritic cells (DCs). Loss of FcRγ or both DAP12 and FcRγ enhanced the maturation and cytokine production in DCs upon Dectin-1 activation compared to normal cells, whereas DCs lacking only DAP12 showed little changes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29033936/coinhibitory-receptor-expression-and-immune-checkpoint-blockade-maintaining-a-balance-in-cd8-t-cell-responses-to-chronic-viral-infections-and-cancer
#11
REVIEW
Isobel S Okoye, Michael Houghton, Lorne Tyrrell, Khaled Barakat, Shokrollah Elahi
In cancer and chronic viral infections, T cells are exposed to persistent antigen stimulation. This results in expression of multiple inhibitory receptors also called "immune checkpoints" by T cells. Although these inhibitory receptors under normal conditions maintain self-tolerance and prevent immunopathology, their sustained expression deteriorates T cell function: a phenomenon called exhaustion. Recent advances in cancer immunotherapy involve blockade of cytotoxic T lymphocyte antigen-4 and programmed cell death 1 in order to reverse T cell exhaustion and reinvigorate immunity, which has translated to dramatic clinical remission in many cases of metastatic melanoma and lung cancer...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29033401/construction-of-c35-gene-bait-recombinants-and-t47d-cell-cdna-library
#12
Kun Yin, Chao Xu, Gui-Hua Zhao, Ye Liu, Ting Xiao, Song Zhu, Ge Yan
C35 is a novel tumor biomarker associated with metastasis progression. To investigate the interaction factors of C35 in its high expressed breast cancer cell lines, we constructed bait recombinant plasmids of C35 gene and T47D cell cDNA library for yeast two-hybrid screening. Full length C35 sequences were subcloned using RT-PCR from cDNA template extracted from T47D cells. Based on functional domain analysis, the full-length C351-348bp was also truncated into two fragments C351-153bp and C35154-348bp to avoid auto-activation...
October 16, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28974577/molecular-mechanisms-for-enhancement-of-stromal-cell-derived-factor-1-induced-chemotaxis-by-platelet-endothelial-cell-adhesion-molecule-1-pecam-1
#13
Yoshihiro Umezawa, Hiroki Akiyama, Keigo Okada, Shinya Ishida, Ayako Nogami, Gaku Oshikawa, Tetsuya Kurosu, Osamu Miura
Platelet endothelial cell adhesion molecule 1 (PECAM-1) is a cell adhesion protein involved in the regulation of cell adhesion and migration. Interestingly, several PECAM-1-deficient hematopoietic cells exhibit impaired chemotactic responses to stromal cell-derived factor 1 (SDF-1), a chemokine essential for B lymphopoiesis and bone marrow myelopoiesis. However, whether PECAM-1 is involved in SDF-1-regulated chemotaxis is unknown. We report here that SDF-1 induces tyrosine phosphorylation of PECAM-1 at its immunoreceptor tyrosine-based inhibition motifs in several hematopoietic cell lines via the Src family kinase Lyn, Bruton's tyrosine kinase, and JAK2 and that inhibition of these kinases reduced chemotaxis...
December 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28945004/tlr3-contributes-to-persistent-autophagy-and-heart-failure-in-mice-after-myocardial-infarction
#14
Ting Gao, Shao-Ping Zhang, Jian-Fei Wang, Li Liu, Yin Wang, Zhi-Yong Cao, Qi-Kuan Hu, Wen-Jun Yuan, Li Lin
Toll-like receptors (TLRs) are essential immunoreceptors involved in host defence against invading microbes. Recent studies indicate that certain TLRs activate immunological autophagy to eliminate microbes. It remains unknown whether TLRs regulate autophagy to play a role in the heart. This study examined this question. The activation of TLR3 in cultured cardiomyocytes was observed to increase protein levels of autophagic components, including LC3-II, a specific marker for autophagy induction, and p62/SQSTM1, an autophagy receptor normally degraded in the final step of autophagy...
September 25, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28923946/immunoreceptor-tyrosine-based-inhibitory-motif-dependent-functions-of-an-mhc-class-i-specific-nk-cell-receptor
#15
Michael D Bern, Diana L Beckman, Takashi Ebihara, Samantha M Taffner, Jennifer Poursine-Laurent, J Michael White, Wayne M Yokoyama
Natural killer (NK) cells express MHC class I (MHC-I)-specific receptors, such as Ly49A, that inhibit killing of cells expressing self-MHC-I. Self-MHC-I also "licenses" NK cells to become responsive to activating stimuli and regulates the surface level of NK-cell inhibitory receptors. However, the mechanisms of action resulting from these interactions of the Ly49s with their MHC-I ligands, particularly in vivo, have been controversial. Definitive studies could be derived from mice with targeted mutations in inhibitory Ly49s, but there are inherent challenges in specifically altering a single gene within a multigene family...
October 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28912774/therapeutic-antibodies-to-kir3dl2-and-other-target-antigens-on-cutaneous-t-cell-lymphomas
#16
REVIEW
Christian Schmitt, Anne Marie-Cardine, Armand Bensussan
KIR3DL2 is a member of the killer cell immunoglobulin-like receptor (KIR) family that was initially identified at the surface of natural killer (NK) cells. KIR3DL2, also known as CD158k, is expressed as a disulfide-linked homodimer. Each chain is composed of three immunoglobulin-like domains and a long cytoplasmic tail containing two immunoreceptor tyrosine-based inhibitory motifs. Beside its expression on NK cells, it is also found on rare circulating T lymphocytes, mainly CD8(+). Although the KIR gene number varies between haplotype, KIR3DL2 is a framework gene present in all individuals...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28893902/the-cytosolic-domain-of-t-cell-receptor-%C3%AE-associates-with-membranes-in-a-dynamic-equilibrium-and-deeply-penetrates-the-bilayer
#17
Kerstin Zimmermann, Rebecca Eells, Frank Heinrich, Stefanie Rintoul, Brian Josey, Prabhanshu Shekhar, Mathias Lösche, Lawrence J Stern
Interactions between lipid bilayers and the membrane-proximal regions of membrane-associated proteins play important roles in regulating membrane protein structure and function. The T-cell antigen receptor is an assembly of eight single-pass membrane-spanning subunits on the surface of T lymphocytes that initiates cytosolic signaling cascades upon binding antigens presented by MHC-family proteins on antigen-presenting cells. Its ζ-subunit contains multiple cytosolic immunoreceptor tyrosine-based activation motifs involved in signal transduction, and this subunit by itself is sufficient to couple extracellular stimuli to intracellular signaling events...
October 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28888895/regulation-of-platelet-activation-and-thrombus-formation-by-reactive-oxygen-species
#18
Jianlin Qiao, Jane F Arthur, Elizabeth E Gardiner, Robert K Andrews, Lingyu Zeng, Kailin Xu
Reactive oxygen species (ROS) are generated within activated platelets and play an important role in regulating platelet responses to collagen and collagen-mediated thrombus formation. As a major collagen receptor, platelet-specific glycoprotein (GP)VI is a member of the immunoglobulin (Ig) superfamily, with two extracellular Ig domains, a mucin domain, a transmembrane domain and a cytoplasmic tail. GPVI forms a functional complex with the Fc receptor γ-chain (FcRγ) that, following receptor dimerization, signals via an intracellular immunoreceptor tyrosine-based activation motif (ITAM), leading to rapid activation of Src family kinase signaling pathways...
September 7, 2017: Redox Biology
https://www.readbyqxmd.com/read/28855691/immunology-balancing-immunoreceptor-signalling
#19
Jessica McHugh
No abstract text is available yet for this article.
October 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28855374/differential-mast-cell-outcomes-are-sensitive-to-fc%C3%AE%C2%B5ri-syk-binding-kinetics
#20
Samantha L Schwartz, Cédric Cleyrat, Mark J Olah, Peter K Relich, Genevieve K Phillips, William S Hlavacek, Keith A Lidke, Bridget S Wilson, Diane S Lidke
Cross-linking of immunoglobulin E-bound FcεRI triggers multiple cellular responses, including degranulation and cytokine production. Signaling is dependent on recruitment of Syk via docking of its dual SH2 domains to phosphorylated tyrosines within the FcεRI immunoreceptor tyrosine-based activation motifs. Using single-molecule imaging in live cells, we directly visualized and quantified the binding of individual mNeonGreen-tagged Syk molecules as they associated with the plasma membrane after FcεRI activation...
November 7, 2017: Molecular Biology of the Cell
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