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https://www.readbyqxmd.com/read/28077173/is-cd47-an-innate-immune-checkpoint-for-tumor-evasion
#1
REVIEW
Xiaojuan Liu, Hyunwoo Kwon, Zihai Li, Yang-Xin Fu
Cluster of differentiation 47 (CD47) (also known as integrin-associated protein) is a ubiquitously expressed glycoprotein of the immunoglobulin superfamily that plays a critical role in self-recognition. Various solid and hematologic cancers exploit CD47 expression in order to evade immunological eradication, and its overexpression is clinically correlated with poor prognoses. One essential mechanism behind CD47-mediated immune evasion is that it can interact with signal regulatory protein-alpha (SIRPα) expressed on myeloid cells, causing phosphorylation of the SIRPα cytoplasmic immunoreceptor tyrosine-based inhibition motifs and recruitment of Src homology 2 domain-containing tyrosine phosphatases to ultimately result in delivering an anti-phagocytic-"don't eat me"-signal...
January 11, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28073159/polymeric-immunoglobulin-receptor-promotes-tumor-growth-in-hepatocellular-carcinoma
#2
Xihua Yue, Jing Ai, Yang Xu, Yi Chen, Min Huang, Xinying Yang, Bo Hu, Haotian Zhang, Changxi He, Xinrong Yang, Weiguo Tang, Xia Peng, Liwei Dong, Hongyang Wang, Jia Fan, Jian Ding, Meiyu Geng
: Deregulation of the immune system is believed to contribute to cancer malignancy, which has led to recent therapeutic breakthroughs facilitating antitumor immunity. In a malignant setting, immunoglobulin receptors, which are fundamental components of the human immune system, fulfill paradoxical roles in cancer pathogenesis. This study describes a previously unrecognized pro-oncogenic function of polymeric immunoglobulin receptor (pIgR) in the promotion of cell transformation and proliferation...
January 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28069953/c-type-lectin-receptor-dcir-modulates-immunity-to-tuberculosis-by-sustaining-type-i-interferon-signaling-in-dendritic-cells
#3
Anthony Troegeler, Ingrid Mercier, Céline Cougoule, Danilo Pietretti, André Colom, Carine Duval, Thien-Phong Vu Manh, Florence Capilla, Renaud Poincloux, Karine Pingris, Jérôme Nigou, Jörg Rademann, Marc Dalod, Frank A W Verreck, Talal Al Saati, Geanncarlo Lugo-Villarino, Bernd Lepenies, Denis Hudrisier, Olivier Neyrolles
Immune response against pathogens is a tightly regulated process that must ensure microbial control while preserving integrity of the infected organs. Tuberculosis (TB) is a paramount example of a chronic infection in which antimicrobial immunity is protective in the vast majority of infected individuals but can become detrimental if not finely tuned. Here, we report that C-type lectin dendritic cell (DC) immunoreceptor (DCIR), a key component in DC homeostasis, is required to modulate lung inflammation and bacterial burden in TB...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27984101/imaging-flow-cytometry-and-gst-pulldown-assays-provide-new-insights-into-channel-catfish-leukocyte-immune-type-receptor-mediated-phagocytic-pathways
#4
Myron A Zwozdesky, Chenjie Fei, Dustin M E Lillico, James L Stafford
Channel catfish (Ictalurus punctatus) leukocyte immune-type receptors (IpLITRs) control various innate immune cell effector responses including the phagocytic process. This large immunoregulatory receptor family also consists of multiple receptor-types with variable signaling abilities that is dependent on their inherent or acquired tyrosine-containing cytoplasmic tail (CYT) regions. For example, IpLITR 2.6b associates with the immunoreceptor tyrosine-based activation motif (ITAM)-containing adaptor molecule IpFcRγ-L, and when expressed in mammalian cells it activates phagocytosis using a similar profile of intracellular signaling mediators that also regulate the prototypical mammalian Fc receptor (FcR) phagocytic pathway...
October 27, 2016: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/27958302/structural-basis-for-human-pecam-1-mediated-trans-homophilic-cell-adhesion
#5
Menglong Hu, Hongmin Zhang, Qun Liu, Quan Hao
Cell adhesion involved in signal transduction, tissue integrity and pathogen infection is mainly mediated by cell adhesion molecules (CAM). One CAM member, platelet-endothelial-cell adhesion molecule-1 (PECAM-1), plays an important role in tight junction among endothelia cells, leukocyte trafficking, and immune response through its homophilic and heterophilic binding patterns. Both kinds of interactions, which lead to endogenous and exogenous signal transmission, are derived from extracellular immunoglobulin-like (IgL) domains and cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) of PECAM-1...
December 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27889398/recognition-of-mycobacterial-lipids-by-immune-receptors
#6
REVIEW
Eri Ishikawa, Daiki Mori, Sho Yamasaki
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), infects one-third of the world's population and causes 1.5 million deaths each year. The cell envelopes of mycobacteria comprise a wealth of unique glycolipids, including trehalose-6,6'-dimycolate (TDM), lipoarabinomannan (LAM), lipomannan (LM), and phosphatidylinositol (PI) mannosides (PIMs). These lipids are important modulators of the host immune responses during infection and in some cases have been used as adjuvants [e.g., complete Freund's adjuvant (CFA)]...
January 2017: Trends in Immunology
https://www.readbyqxmd.com/read/27836913/immunoreceptor-cd300a-on-mast-cells-and-dendritic-cells-regulates-neutrophil-recruitment-in-a-murine-model-of-sepsis
#7
Kankanam Gamage Sanath Udayanga, Yoshiyuki Nakamura, Chigusa Nakahashi-Oda, Akira Shibuya
Sepsis is a life-threatening syndrome caused by abnormal host immune responses against bacterial infection. Although innate immune cells are known to be important in the pathogenesis of sepsis, how their activation is regulated during sepsis remains incompletely understood. Here, we examined the role of the inhibitory immunoreceptor CD300a, which is expressed on various types of myeloid cells, in the pathogenesis of sepsis induced by cecal ligation and puncture (CLP). To this end, we used mice in which CD300a was specifically deleted on mast cells (MCs; Cd300a (fl/fl) Mcpt5-Cre), dendritic cells (DCs; Cd300a (fl/fl) Itgax-Cre), or macrophages and neutrophils (Cd300a (fl/fl) Lyz2-Cre)...
December 2016: International Immunology
https://www.readbyqxmd.com/read/27795427/the-glycoprotein-b-cytoplasmic-domain-lysine-cluster-is-critical-for-varicella-zoster-virus-cell-cell-fusion-regulation-and-infection
#8
Edward Yang, Ann M Arvin, Stefan L Oliver
: The conserved glycoproteins gB and gH-gL are essential for herpesvirus entry and cell-cell fusion induced syncytium formation, a characteristic of varicella-zoster virus (VZV) pathology in skin and sensory ganglia. VZV syncytium formation, which has been implicated in the painful condition of postherpetic neuralgia, is regulated by the cytoplasmic domains of gB (gBcyt) via an immunoreceptor tyrosine-based inhibition motif (ITIM) and gH (gHcyt). A lysine cluster (K894, K897, K898, and K900) in the VZV gBcyt was identified by sequence alignment to be conserved among alphaherpesviruses, suggesting a functional role...
January 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27746174/dendritic-cell-inhibitory-receptor-4-dcir4-is-preferentially-expressed-on-inflammatory-and-patrolling-monocytes
#9
Yosuke Kameda, Motoki Hanayama, Atsushi Kishimoto, Masahiko Kume, Kazuo Yamamoto, Naoki Matsumoto
Dendritic cell inhibitory receptor 4 (DCIR4, Clec4a1) is a lectin receptor and a member of mouse dendritic cell immunoreceptor family. Due to the lack of antibodies against DCIR4, expression of DCIR4 protein remains unknown. In this study, we established a specific monoclonal antibody against DCIR4 and investigated the expression of DCIR4 among immune cells. We found that DCIR4 was expressed on non-granulocytic subsets of CD11b(+) cells in various immune organs including bone marrow, peripheral blood, spleen, skin-associated lymph nodes and mesenteric lymph nodes...
October 13, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27742834/tolerogenic-immunoreceptor-ilt3-lilrb4-paradoxically-marks-pathogenic-auto-antibody-producing-plasmablasts-and-plasma-cells-in-non-treated-sle
#10
Masanori Inui, Akiko Sugahara-Tobinai, Hiroshi Fujii, Ari Itoh-Nakadai, Hidehiro Fukuyama, Tomohiro Kurosaki, Tomonori Ishii, Hideo Harigae, Toshiyuki Takai
Plasmablasts and plasma cells (PBs and PCs) producing pathogenic auto-antibodies in patients with systemic autoimmune diseases could be a better target for specific therapies for the disease than general immunosuppression or pan- or activated B-cell targeting. Our previous study indicated that leukocyte immunoglobulin-like receptor (LILR) B4 (B4, also known as ILT3/LIR-5/CD85k), a tolerogenic receptor in antigen-presenting cells, is ectopically expressed on the PB/PC surface in healthy individuals. Here, we show that the enlarged population size of PBs/PCs with augmented B4 expression is characteristic in non-treated systemic lupus erythematosus (SLE)...
December 2016: International Immunology
https://www.readbyqxmd.com/read/27723141/dendritic-cell-specific-transmembrane-protein-dc-stamp-regulates-osteoclast-differentiation-via-the-ca2-nfatc1-axis
#11
Ya-Hui Chiu, Edward Schwarz, Dongge Li, Yuexin Xu, Tzong-Ren Sheu, Jinbo Li, Karen L de Mesy Bentley, Changyong Feng, Baoli Wang, Jhih-Cheng Wang, Liz Albertorio-Saez, Ronald Wood, Minsoo Kim, Wensheng Wang, Christopher T Ritchlin
DC-STAMP is a multi-pass transmembrane protein essential for cell-cell fusion of osteoclast precursors during osteoclast (OC) development. DC-STAMP-/- mice have mild osteopetrosis and form mononuclear cells with limited resorption capacity. The identification of an Immunoreceptor Tyrosine-based Inhibitory Motif (ITIM) on the cytoplasmic tail of DC-STAMP suggested a potential signaling function but the absence of known DC-STAMP ligand has hindered examination of downstream signaling pathways. To address this problem, we engineered a light-activatable DC-STAMP chimeric molecule in which light exposure mimics ligand engagement that can be traced by downstream Ca2+ signaling...
October 10, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27696702/distinct-roles-of-immunoreceptor-tyrosine-based-motifs-in-immunosuppressive-indoleamine-2-3-dioxygenase-1
#12
Elisa Albini, Verdiana Rosini, Marco Gargaro, Giada Mondanelli, Maria L Belladonna, Maria Teresa Pallotta, Claudia Volpi, Francesca Fallarino, Antonio Macchiarulo, Cinzia Antognelli, Roberta Bianchi, Carmine Vacca, Paolo Puccetti, Ursula Grohmann, Ciriana Orabona
The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) catalyses the initial, rate-limiting step in tryptophan (Trp) degradation, resulting in tryptophan starvation and the production of immunoregulatory kynurenines. IDO1's catalytic function has long been considered as the one mechanism responsible for IDO1-dependent immune suppression by dendritic cells (DCs), which are master regulators of the balance between immunity and tolerance. However, IDO1 also harbours immunoreceptor tyrosine-based inhibitory motifs, (ITIM1 and ITIM2), that, once phosphorylated, bind protein tyrosine phosphatases, (SHP-1 and SHP-2), and thus trigger an immunoregulatory signalling in DCs...
January 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27695943/the-role-of-cea-related-cell-adhesion-molecule-1-ceacam1-in-vascular-homeostasis
#13
REVIEW
Uwe Rueckschloss, Stefanie Kuerten, Süleyman Ergün
Carcinoembryonic antigen (CEA)-related cell adhesion molecules belong to the immunoglobulin superfamily, are expressed in a broad spectrum of tissues and cell types and exert context-dependent activating as well as inhibitory effects. Among these molecules, the CEA-related cell adhesion molecule-1 (CEACAM1) is a transmembrane molecule with an extracellular, a transmembrane and a cytoplasmic domain. The latter contains immunoreceptor tyrosine-based inhibitory motifs and functions as a signaling molecule. CEACAM1 can form homo- and heterodimers which is relevant for its signaling activities...
December 2016: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/27694038/targeting-mast-cells-uncovering-prolific-therapeutic-role-in-myriad-diseases
#14
REVIEW
Jatinder Singh, Ramanpreet Shah, Dhandeep Singh
The mast cells are integral part of immune system and they have pleiotropic physiological functions in our body. Any type of abnormal stimuli causes the mast cells receptors to spur the otherwise innocuous mast cells to degranulate and release inflammatory mediators like histamine, cytokines, chemokines and prostaglandins. These mediators are involved in various diseases like allergy, asthma, mastocytosis, cardiovascular disorders, etc. Herein, we describe the receptors involved in degranulation of mast cells and are broadly divided into four categories: G-protein coupled receptors, ligand gated ion channels, immunoreceptors and pattern recognition receptors...
November 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27630214/regulation-of-fcr%C3%AE-function-by-site-specific-serine-phosphorylation
#15
Spandan Shah, Andrew W Gibson, Chuanyi Ji, Eric Darrington, James Mobley, Kyoko Kojima, Jeffrey C Edberg, Robert P Kimberly
The common FcRγ, an immunoreceptor tyrosine-based activation motif (ITAM)- containing adaptor protein, associates with multiple leukocyte receptor complexes and mediates signal transduction through the ITAM in the cytoplasmic domain. The presence of multiple serine and threonine residues within this motif suggests the potential for serine/threonine phosphorylation in modulating signaling events. Single-site mutational analysis of these residues in RBL-2H3 cells indicates that each may contribute to net FcRγ-mediated signaling, and mass spectrometry of WT human FcRγ from receptor-stimulated cells shows consistent preferential phosphorylation of the serine residue at position 51...
September 14, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27578867/cd47-sirp%C3%AE-interaction-and-il-10-constrain-inflammation-induced-macrophage-phagocytosis-of-healthy-self-cells
#16
Zhen Bian, Lei Shi, Ya-Lan Guo, Zhiyuan Lv, Cong Tang, Shuo Niu, Alexandra Tremblay, Mahathi Venkataramani, Courtney Culpepper, Limin Li, Zhen Zhou, Ahmed Mansour, Yongliang Zhang, Andrew Gewirtz, Koby Kidder, Ke Zen, Yuan Liu
Rapid clearance of adoptively transferred Cd47-null (Cd47(-/-)) cells in congeneic WT mice suggests a critical self-recognition mechanism, in which CD47 is the ubiquitous marker of self, and its interaction with macrophage signal regulatory protein α (SIRPα) triggers inhibitory signaling through SIRPα cytoplasmic immunoreceptor tyrosine-based inhibition motifs and tyrosine phosphatase SHP-1/2. However, instead of displaying self-destruction phenotypes, Cd47(-/-) mice manifest no, or only mild, macrophage phagocytosis toward self-cells except under the nonobese diabetic background...
September 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27569911/nuclear-pore-permeabilization-is-a-convergent-signaling-event-in-effector-triggered-immunity
#17
Yangnan Gu, Sophia G Zebell, Zizhen Liang, Shui Wang, Byung-Ho Kang, Xinnian Dong
Nuclear transport of immune receptors, signal transducers, and transcription factors is an essential regulatory mechanism for immune activation. Whether and how this process is regulated at the level of the nuclear pore complex (NPC) remains unclear. Here, we report that CPR5, which plays a key inhibitory role in effector-triggered immunity (ETI) and programmed cell death (PCD) in plants, is a novel transmembrane nucleoporin. CPR5 associates with anchors of the NPC selective barrier to constrain nuclear access of signaling cargos and sequesters cyclin-dependent kinase inhibitors (CKIs) involved in ETI signal transduction...
September 8, 2016: Cell
https://www.readbyqxmd.com/read/27558333/regulation-of-neutrophil-functions-through-inhibitory-receptors-an-emerging-paradigm-in-health-and-disease
#18
REVIEW
Benoit Favier
Neutrophils are the most abundant subset of leukocytes and play a crucial role in the immune responses against the daily pathogen attacks faced by the host. Neutrophils exhibit several functions for fighting microbes, including the release of granules containing highly toxic molecules, the production of reactive oxygen species and inflammatory cytokines as well as NETosis. Therefore, immune responses mediated by neutrophils must be tightly regulated to protect the host from pathogen assaults without inducing detrimental inflammation and tissue damage...
September 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27550373/the-dok-3-grb2-adaptor-module-promotes-inducible-association-of-the-lipid-phosphatase-ship-with-the-bcr-in-a-coreceptor-independent-manner
#19
Birgit Manno, Thomas Oellerich, Tim Schnyder, Jasmin Corso, Marion Lösing, Konstantin Neumann, Henning Urlaub, Facundo D Batista, Michael Engelke, Jürgen Wienands
The SH2 domain-containing inositol 5'-phosphatase (SHIP) plays a key role in preventing autoimmune phenomena by limiting antigen-mediated B cell activation. SHIP function is thought to require the dual engagement of the BCR and negative regulatory coreceptors as only the latter appear capable of recruiting SHIP from the cytosol to the plasma membrane by virtue of phosphorylated immunoreceptor tyrosine-based inhibitory motifs. Here we demonstrate a coreceptor-independent membrane recruitment and function of SHIP in B cells...
August 23, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27456487/fc%C3%AE-riib-independent-mechanisms-controlling-membrane-localization-of-the-inhibitory-phosphatase-ship-in-human-b-cells
#20
Samantha D Pauls, Arnab Ray, Sen Hou, Andrew T Vaughan, Mark S Cragg, Aaron J Marshall
SHIP is an important regulator of immune cell signaling that functions to dephosphorylate the phosphoinositide phosphatidylinositol 3,4,5-trisphosphate at the plasma membrane and mediate protein-protein interactions. One established paradigm for SHIP activation involves its recruitment to the phospho-ITIM motif of the inhibitory receptor FcγRIIB. Although SHIP is essential for the inhibitory function of FcγRIIB, it also has critical modulating functions in signaling initiated from activating immunoreceptors such as B cell Ag receptor...
September 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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