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https://www.readbyqxmd.com/read/28332308/ceacam1-long-isoform-has-opposite-effects-on-the-growth-of-human-mastocytosis-and-medullary-thyroid-carcinoma-cells
#1
Chiyuki Ueshima, Tatsuki R Kataoka, Yusuke Takei, Masahiro Hirata, Akihiko Sugimoto, Mitsuyoshi Hirokawa, Yoshimichi Okayama, Richard S Blumberg, Hironori Haga
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed in a number of tumor cell types. The immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing isoforms of this molecule which possess a long cytoplasmic tail (CEACAM1-L) generally play inhibitory roles in cell function by interacting with Src homology 2 domain-containing tyrosine phosphatase (SHP)-1 and/or SHP-2. Src family kinases (SFKs) are also known to bind to and phosphorylate CEACAM1-L isoforms. Here, we report that CEACAM1 was uniquely expressed at high levels in both human neoplastic mast cells (mastocytosis) and medullary thyroid carcinoma cell (MTC) lines, when compared with their expression in nonneoplastic mast cells or nonneoplastic C cells...
March 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28127756/absence-of-dcir1-reduces-the-mortality-rate-of-endotoxemic-hepatitis-in-mice
#2
Toshifumi Ishiguro, Testuya Fukawa, Kotaro Akaki, Koji Nagaoka, Tatsuki Takeda, Yoichiro Iwakura, Kayo Inaba, Kazuhiko Takahara
Dendritic cell immunoreceptor (DCIR) is a C-type lectin with an immunoreceptor tyrosine-based inhibitory motif (ITIM). Mice lacking DCIR1 (Dcir1(-/-) mice) show higher susceptibility to chronic arthritis with increasing age, suggesting that DCIR1 is involved in immune modulation via its ITIM. However, the role of DCIR1 in acute immune responses is not clear. In this study, we explored its role in acute experimental hepatitis. Upon injection of d-galactosamine and lipopolysaccharide, Dcir1(-/-) mice showed decreased mortality rates and serum levels of alanine aminotransferase (ALT)...
January 26, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28108989/tigit-signalling-pathway-negatively-regulates-cd4-t-cell-responses-in-systemic-lupus-erythematosus
#3
Lie Mao, Hongyan Hou, Shiji Wu, Yu Zhou, Juan Wang, Jing Yu, Xiaohui Wu, Yanfang Lu, Liyan Mao, Munyemana Jean Bosco, Feng Wang, Ziyong Sun
B-lymphocyte hyperactivity in systemic lupus erythematosus (SLE) is T-cell-dependent, and CD4(+) T-cell activation is essential to SLE pathogenesis. However, the mechanism of the deregulation of CD4(+) T cells in SLE is largely unknown. T-cell immunoglobulin and ITIM domain (TIGIT) is a new inhibitory receptor preferentially expressed on activated CD4(+) T cells. Here, we address the role of TIGIT in the pathogenesis of SLE. Our results showed that TIGIT expression on CD4(+) T cells was significantly elevated in patients with SLE and highly correlated with the activity of the disease...
January 20, 2017: Immunology
https://www.readbyqxmd.com/read/28089363/pertussis-toxin-targets-the-innate-immunity-through-dap12-fcr%C3%AE-and-myd88-adaptor-proteins
#4
Vongsavanh Phongsisay, Ei'ichi Iizasa, Hiromitsu Hara, Hiroki Yoshida
Activation of the innate immunity by adjuvants, such as pertussis toxin (PTX), in the presence of autoreactive lymphocytes and antigen mimicry is sufficient to trigger autoimmunity. Toll-like, C-type lectin, and immunglobulin-like receptors play an important role in the innate immunity by sensing a variety of microbial products through several adaptor proteins, including MyD88, DAP12, and FcRγ. This study investigated the interaction between PTX and innate immune components. The direct interactions between coated PTX and receptor-fusion proteins were examined using ELISA-based binding assays...
December 30, 2016: Immunobiology
https://www.readbyqxmd.com/read/28046066/htlv-1-bzip-factor-enhances-t-cell-proliferation-by-impeding-the-suppressive-signaling-of-co-inhibitory-receptors
#5
Haruka Kinosada, Jun-Ichirou Yasunaga, Kazuya Shimura, Paola Miyazato, Chiho Onishi, Tomonori Iyoda, Kayo Inaba, Masao Matsuoka
Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia-lymphoma (ATL) and inflammatory diseases. To enhance cell-to-cell transmission of HTLV-1, the virus increases the number of infected cells in vivo. HTLV-1 bZIP factor (HBZ) is constitutively expressed in HTLV-1 infected cells and ATL cells and promotes T-cell proliferation. However, the detailed mechanism by which it does so remains unknown. Here, we show that HBZ enhances the proliferation of expressing T cells after stimulation via the T-cell receptor...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28030587/cd5-ck2-signaling-modulates-erk-activation-and-thymocyte-survival
#6
Carlos A Mier-Aguilar, Kevin S Cashman, Chander Raman, Gloria Soldevila
CD5 is well recognized for its importance in thymic selection. Although this property of CD5 has been attributed to its ITIM-domain dependent regulation of TCR-signal strength, the mechanism has not been established. A second major signaling domain within the cytoplasmic tail of CD5 is a CK2 binding/activation domain (CD5-CK2BD). Using a gene-targeted mouse in which the CD5-CK2BD is selectively ablated (CD5-ΔCK2BD), we determined that loss of function of CD5-CK2 signaling in a MHC-II selecting TCR transgenic (OT-II) mouse resulted in decrease in double positive (DP) thymocytes, which correlated with enhanced apoptosis...
2016: PloS One
https://www.readbyqxmd.com/read/27978489/structural-mutational-and-biophysical-studies-reveal-a-canonical-mode-of-molecular-recognition-between-immune-receptor-tigit-and-nectin-2
#7
Dibyendu Samanta, Haisu Guo, Rotem Rubinstein, Udupi A Ramagopal, Steven C Almo
In addition to antigen-specific stimulation of T cell receptor (TCR) by a peptide-MHC complex, the functional outcome of TCR engagement is regulated by antigen-independent costimulatory signals. Costimulatory signals are provided by an array of interactions involving activating and inhibitory receptors expressed on T cells and their cognate ligands on antigen presenting cells. T cell immunoglobulin and ITIM domain (TIGIT), a recently identified immune receptor expressed on T and NK cells, upon interaction with either of its two ligands, nectin-2 or poliovirus receptor (PVR), inhibits activation of T and NK cells...
January 2017: Molecular Immunology
https://www.readbyqxmd.com/read/27958302/structural-basis-for-human-pecam-1-mediated-trans-homophilic-cell-adhesion
#8
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/27932517/allergin-1-inhibits-tlr2-mediated-mast-cell-activation-and-suppresses-dermatitis
#9
Satoshi Tsurusaki, Satoko Tahara-Hanaoka, Shohei Shibagaki, Shota Miyake, Masamichi Imai, Shiro Shibayama, Masato Kubo, Akira Shibuya
TLR2 recognizes cell wall components of Staphylococcus aureus, which colonizes >90% of atopic eczematous skin lesions. The regulatory mechanisms of TLR2 signaling in the skin remain unclear. Allergin-1, an inhibitory immunoglobulin-like receptor containing an ITIM, is expressed on mast cells (MCs) and inhibits IgE-mediated anaphylaxis in mice. Here, we show that Allergin-1 inhibits TLR2-mediated activation of, and inflammatory cytokine production by, MCs in vitro Compared with wild-type mice, Allergin-1-deficient mice showed enhanced ear swelling with enhanced collagen deposition and greater Ly6G(+) neutrophil recruitment after intra-dermal injection of Pam2CSK4 into pinnae...
December 2016: International Immunology
https://www.readbyqxmd.com/read/27852220/coevolution-of-paired-receptors-in-xenopus-carcinoembryonic-antigen-related-cell-adhesion-molecule-families-suggests-appropriation-as-pathogen-receptors
#10
Wolfgang Zimmermann, Robert Kammerer
BACKGROUND: In mammals, CEACAM1 and closely related members represent paired receptors with similar extracellular ligand-binding regions and cytoplasmic domains with opposing functions. Human CEACAM1 and CEACAM3 which have inhibitory ITIM/ITSM and activating ITAM-like motifs, respectively, in their cytoplasmic regions are such paired receptors. Various bacterial pathogens bind to CEACAM1 on epithelial and immune cells facilitating both entry into the host and down-regulation of the immune response whereas interaction with granulocyte-specific CEACAM3 leads to their uptake and destruction...
November 16, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27819527/tigit-a-novel-therapeutic-target-for-tumor-immunotherapy
#11
REVIEW
Xin-Guang Liu, Ming Hou, Yu Liu
Co-inhibitory and co-stimulatory receptors act in concert to regulate adaptive immune cell function, and the balance of these receptors is essential for the maintenance of immune homeostasis. Tumors constitute highly suppressive microenvironments in which elevated expression of co-inhibitory receptors on tumor-infiltrating lymphocytes (TILs) is often found. Functional blockade of the co-inhibitory receptors such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) have yielded encouraging outcomes in tumors, generating substantial interest in seeking for additional co-inhibitory molecules that may act as potential interfering targets...
February 2017: Immunological Investigations
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
#12
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/27762335/an-inhibitory-receptor-of-vlrb-in-the-agnathan-lamprey
#13
Fenfang Wu, Liyong Chen, Yong Ren, Xiaojing Yang, Tongzhou Yu, Bo Feng, Shangwu Chen, Anlong Xu
Lamprey, the primitive jawless vertebrate, uses variable lymphocyte receptor (VLR) as alternative adaptive immune system instead of immunoglobulin (Ig)-based receptors used in jawed vertebrates. In the present study, we characterized a potential inhibitory receptor of VLRB from leucocytes in lamprey. It is a novel ITIM-containing IgSF protein and was therefore named as NICIP. NICIP has two Ig-like domains in extracellular region, a transmembrane domain and two classical ITIM motifs in cytoplasmic domain. It is mainly expressed on the surface of granulocytes and monocytes and can interact with VLRB...
October 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27723141/dendritic-cell-specific-transmembrane-protein-dc-stamp-regulates-osteoclast-differentiation-via-the-ca2-nfatc1-axis
#14
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
#15
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/27577071/expression-of-immune-checkpoints-in-t-cells-of-esophageal-cancer-patients
#16
Jinhua Xie, Ji Wang, Shouliang Cheng, Liangfeng Zheng, Feiyue Ji, Lin Yang, Yan Zhang, Haoming Ji
Inhibition of immune checkpoint proteins (checkpoints) has become a promising anti-esophageal cancer strategy. We here tested expressions of immune checkpoints in human esophageal cancers. Our results showed the expressions of many immune checkpoints, including CD28, CD27, CD137L, programmed death 1 (PD-1), T cell immunoglobulin mucin-3 (TIM-3), T cell Ig and ITIM domain (TIGIT), CD160, cytotoxic T lymphocyte antigen 4 (CTLA-4), CD200, CD137 and CD158, were dysregulated in peripheral T cells of esophageal cancer patients...
September 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27558333/regulation-of-neutrophil-functions-through-inhibitory-receptors-an-emerging-paradigm-in-health-and-disease
#17
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/27506283/local-lateral-environment-of-the-molecules-at-the-surface-of-dmso-water-mixtures
#18
Balázs Fábián, Abdenacer Idrissi, Bogdan Marekha, Pál Jedlovszky
Molecular dynamics simulations of the liquid-vapour interface of dimethyl sulphoxide (DMSO)-water mixtures of 11 different compositions, including two neat systems are performed on the canonical (N, V, T) ensemble at 298 K. The molecules constituting the surface layer of these systems are selected by means of the identification of the truly interfacial molecules (ITIM) method, and their local lateral environment at the liquid surface is investigated by performing Voronoi analysis. The obtained results reveal that both molecules prefer to be in a mixed local environment, consisting of both kinds of molecules, at the liquid surface, and this preference is even stronger here than in the bulk liquid phase...
October 12, 2016: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/27456487/fc%C3%AE-riib-independent-mechanisms-controlling-membrane-localization-of-the-inhibitory-phosphatase-ship-in-human-b-cells
#19
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
https://www.readbyqxmd.com/read/27446638/fc-receptor-like-proteins-in-pathophysiology-of-b-cell-disorder
#20
Mollie Capone, John Matthew Bryant, Natalie Sutkowski, Azizul Haque
Members of the family of Fc receptor-like (FcRL) proteins, homologous to FcγRI, have been identified by multiple research groups. Consequently, they have been described using multiple nomenclatures including Fc receptor homologs (FcRH), immunoglobulin superfamily receptor translocation-associated genes (IRTA), immunoglobulin-Fc-gp42-related genes (IFGP), Src homology 2 domain-containing phosphatase anchor proteins (SPAP), and B cell cross-linked by anti-immunoglobulin M-activating sequences (BXMAS). They are now referred to under a unified nomenclature as FCRL...
June 2016: Journal of Clinical & Cellular Immunology
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