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https://www.readbyqxmd.com/read/29766368/systemic-contact-dermatitis
#1
REVIEW
Marcella Aquino, Greg Rosner
Systemic contact dermatitis (SCD) traditionally refers to a skin condition where an individual who is cutaneously sensitized to an allergen will subsequently react to that same allergen or a cross reacting allergen via a different route. It occurs to allergens including metals, medications, and foods. The exact pathophysiology underlying this disease remains unknown, although it appears to be mediated by type 4 hypersensitivity reactions and possibly type 3 hypersensitivity reactions. The p-I concept (pharmacologic interaction with immunoreceptors) hypothesized that drugs are able to bind directly to a T cell receptor without first being presented by MHC (major histocompatibility complex) molecules and without prior metabolism, which would help explain why SCD can be seen on first exposure to medications...
May 15, 2018: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29757143/tumor-derived-csf-1-induces-the-nkg2d-ligand-rae-1%C3%AE-on-tumor-infiltrating-macrophages
#2
Thornton W Thompson, Benjamin T Jackson, P Jonathan Li, Jiaxi Wang, Alexander Byungsuk Kim, Kristen Ting Hui Huang, Lily Zhang, David H Raulet
NKG2D is an important immunoreceptor expressed on the surface of NK cells and some T cells. NKG2D recognizes a set of ligands typically expressed on infected or transformed cells, but recent studies have also documented NKG2D ligands on subsets of host non-tumor cells in tumor-bearing animals and humans. Here we show that in transplanted tumors and genetically engineered mouse cancer models, tumor-associated macrophages are induced to express the NKG2D ligand RAE-1δ. We find that a soluble factor produced by tumor cells is responsible for macrophage RAE-1δ induction, and we identify tumor-derived colony-stimulating factor-1 (CSF-1) as necessary and sufficient for macrophage RAE-1δ induction in vitro and in vivo ...
May 14, 2018: ELife
https://www.readbyqxmd.com/read/29742762/advantages-of-molecular-weight-identification-during-native-ms-screening
#3
Ahad Khan, Anne Bresnick, Sean Cahill, Mark Girvin, Steve Almo, Ronald Quinn
Native mass spectrometry detection of ligand-protein complexes allowed rapid detection of natural product binders of apo and calcium-bound S100A4 (a member of the metal binding protein S100 family), T cell/transmembrane, immunoglobulin (Ig), and mucin protein 3, and T cell immunoreceptor with Ig and ITIM (immunoreceptor tyrosine-based inhibitory motif) domains precursor protein from extracts and fractions. Based on molecular weight common hits were detected binding to all four proteins. Seven common hits were identified as apigenin 6- C - β - D -glucoside 8- C - α - L -arabinoside, sweroside, 4',5-dihydroxy-7-methoxyflavanone-6- C -rutinoside, loganin acid, 6- C -glucosylnaringenin, biochanin A 7- O -rutinoside and quercetin 3- O -rutinoside...
May 9, 2018: Planta Medica
https://www.readbyqxmd.com/read/29686683/high-affinity-ligands-can-trigger-t-cell-receptor-signaling-without-cd45-segregation
#4
Mohammad Ameen Al-Aghbar, Yeh-Shiu Chu, Bing-Mae Chen, Steve R Roffler
How T cell receptors (TCRs) are triggered to start signaling is still not fully understood. It has been proposed that segregation of the large membrane tyrosine phosphatase CD45 from engaged TCRs initiates signaling by favoring phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) in the cytoplasmic domains of CD3 molecules. However, whether CD45 segregation is important to initiate triggering is still uncertain. We examined CD45 segregation from TCRs engaged to anti-CD3 scFv with high or low affinity and with defined molecular lengths on glass-supported lipid bilayers using total internal reflection microscopy...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29685989/tcr%C3%AE-combinatorial-immunoreceptor-expression-by-neutrophils-correlates-with-parasite-burden-and-enhanced-phagocytosis-during-a-plasmodium-berghei-anka-malaria-infection
#5
Joanna K Chorazeczewski, Maya Aleshnick, Victoria Majam, Winter A Okoth, Regina Kurapova, Adovi Akue, Mark KuKuruga, Sanjai Kumar, Miranda S Oakley
Recent studies have demonstrated that a subpopulation of neutrophils express the TCRαβ combinatorial immunoreceptor in humans and mice. Here, we report that a Plasmodium berghei ANKA murine malaria infection induces expansion of TCRβ expressing CD11b+ Ly6G+ neutrophils in the spleen during the early phase of infection. Measurement of TCRβ transcript and protein levels of neutrophils in wildtype versus nude and Rag1 KO mice establishes that the observed expression is not a consequence of nonspecific antibody staining or passive receptor expression due to phagocytosis or trogocytosis of peripheral T cells...
April 23, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29681901/putting-on-the-brakes-regulatory-kinases-and-phosphatases-maintaining-b-cell-anergy
#6
REVIEW
S Elizabeth Franks, John C Cambier
B cell antigen receptor (BCR) signaling is a tightly regulated process governed by both positive and negative mediators/regulators to ensure appropriate responses to exogenous and autologous antigens. Upon naïve B cell recognition of antigen CD79 [the immunoreceptor tyrosine-based activation motif (ITAM)-containing signaling subunit of the BCR] is phosphorylated and recruits Src and Syk family kinases that then phosphorylate proximal intermediaries linked to downstream activating signaling circuitry. This plasma membrane localized signalosome activates PI3K leading to generation of PIP3 critical for membrane localization and activation of plecktrin homology domain-containing effectors...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29669863/continuous-signaling-of-cd79b-and-cd19-is-required-for-the-fitness-of-burkitt-lymphoma-b-cells
#7
Xiaocui He, Kathrin Kläsener, Joseena M Iype, Martin Becker, Palash C Maity, Marco Cavallari, Peter J Nielsen, Jianying Yang, Michael Reth
Expression of the B-cell antigen receptor (BCR) is essential not only for the development but also for the maintenance of mature B cells. Similarly, many B-cell lymphomas, including Burkitt lymphoma (BL), require continuous BCR signaling for their tumor growth. This growth is driven by immunoreceptor tyrosine-based activation motif (ITAM) and PI3 kinase (PI3K) signaling. Here, we employ CRISPR/Cas9 to delete BCR and B-cell co-receptor genes in the human BL cell line Ramos. We find that Ramos B cells require the expression of the BCR signaling component Igβ (CD79b), and the co-receptor CD19, for their fitness and competitive growth in culture...
April 18, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29669741/shp-1-regulates-hematopoietic-stem-cell-quiescence-by-coordinating-tgf-%C3%AE-signaling
#8
Linjia Jiang, Xue Han, Jin Wang, Chen Wang, Xiaoqiang Sun, Jiayi Xie, Guojin Wu, Hiep Phan, Zhenguo Liu, ChengCheng Zhang, Meng Zhao, Xunlei Kang
Cell cycle quiescence is critical for hematopoietic stem cell (HSC) maintenance. TGF-β signaling in bone marrow niche has been identified in regulating HSC quiescence; however, the intrinsic regulatory mechanisms remain unclear. This study reports that Shp-1 knockout HSCs have attenuated quiescence and impaired long-term self-renewal. SHP-1-activated HSCs are surrounded by megakaryocytes, which regulate HSC quiescence by producing TGF-β1. Mechanistically, SHP-1 interacts with the immunoreceptor tyrosine-based inhibition motif on TGF-β receptor 1 and is critical for TGF-β signaling activation in HSCs...
April 18, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29662641/signaling-lymphocytic-activation-molecules-slam-and-cancers-friends-or-foes
#9
REVIEW
Gregory Fouquet, Ingrid Marcq, Véronique Debuysscher, Jagadeesh Bayry, Amrathlal Rabbind Singh, Abderrahmane Bengrine, Eric Nguyen-Khac, Mickael Naassila, Hicham Bouhlal
Signaling Lymphocytic Activation Molecules (SLAM) family receptors are initially described in immune cells. These receptors recruit both activating and inhibitory SH2 domain containing proteins through their Immunoreceptor Tyrosine based Switch Motifs (ITSMs). Accumulating evidence suggest that the members of this family are intimately involved in different physiological and pathophysiological events such as regulation of immune responses and entry pathways of certain viruses. Recently, other functions of SLAM, principally in the pathophysiology of neoplastic transformations have also been deciphered...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29648914/tx99-is-a-neutralizing-monoclonal-antibody-against-mouse-tigit
#10
Yuho Nakamura, Keisuke Naito, Yumi Yamashita-Kanemaru, Daisuke Komori, Rei Hirochika, Akira Shibuya, Kazuko Shibuya
T cell immunoglobulin and ITIM domains (TIGIT) is an inhibitory immunoreceptor expressed on NK cells, effector and memory T cells, and regulatory T cells (Tregs). The ligands for TIGIT are CD155 (PVR) and CD112 (PVRL2, nectin-2), which are broadly expressed on hematopoietic cells and nonhematopoietic cells. TIGIT negatively regulates antitumor responses, but promotes autoimmune reaction. Although neutralizing anti-human TIGIT mAbs are under clinical trials for cancers, how the blockade of TIGIT interaction with the ligands shows tumor immunity still remains unclear...
April 12, 2018: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/29544443/alternative-splicing-after-gene-duplication-drives-ceacam1-paralog-diversification-in-the-horse
#11
Sophie Mißbach, Denis Aleksic, Lisa Blaschke, Timm Hassemer, Kyung Jin Lee, Martin Mansfeld, Jana Hänske, Johannes Handler, Robert Kammerer
BACKGROUND: The CEA gene family is one of the most rapidly evolving gene families in the human genome. The founder gene of the family is thought to be an ancestor of the inhibitory immune checkpoint molecule CEACAM1. Comprehensive analyses of mammalian genomes showed that the CEA gene family is subject to tremendous gene family expansion and contraction events in different mammalian species. While in some species (e.g. rabbits) less than three CEACAM1 related genes exist, were in others (certain microbat species) up to 100 CEACAM1 paralogs identified...
March 15, 2018: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/29531651/elotuzumab-for-the-treatment-of-relapsed-or-refractory-multiple-myeloma-with-special-reference-to-its-modes-of-action-and-slamf7-signaling
#12
REVIEW
Masafumi Taniwaki, Mihoko Yoshida, Yosuke Matsumoto, Kazuho Shimura, Junya Kuroda, Hiroto Kaneko
Elotuzumab, targeting signaling lymphocytic activation molecule family 7 (SLAMF7), has been approved in combination with lenalidomide and dexamethasone (ELd) for relapsed/refractory multiple myeloma (MM) based on the findings of the phase III randomized trial ELOQUENT-2 (NCT01239797). Four-year follow-up analyses of ELOQUENT-2 have demonstrated that progression-free survival was 21% in ELd versus 14% in Ld. Elotuzumab binds a unique epitope on the membrane IgC2 domain of SLAMF7, exhibiting a dual mechanism of action: natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and enhancement of NK cell activity...
2018: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/29523808/grb2-and-grap-connect-the-b-cell-antigen-receptor-to-erk-map-kinase-activation-in-human-b-cells
#13
Kanika Vanshylla, Caren Bartsch, Christoffer Hitzing, Laura Krümpelmann, Jürgen Wienands, Niklas Engels
The B cell antigen receptor (BCR) employs enzymatically inactive adaptor proteins to facilitate activation of intracellular signaling pathways. In animal model systems, adaptor proteins of the growth factor receptor-bound 2 (Grb2) family have been shown to serve critical functions in lymphocytes. However, the roles of Grb2 and the Grb2-related adaptor protein (GRAP) in human B lymphocytes remain unclear. Using TALEN-mediated gene targeting, we show that in human B cells Grb2 and GRAP amplify signaling by the immunoglobulin tail tyrosine (ITT) motif of mIgE-containing BCRs and furthermore connect immunoreceptor tyrosine-based activation motif (ITAM) signaling to activation of the Ras-controlled Erk MAP kinase pathway...
March 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29512870/dw2008s-and-its-major-constituents-from-justicia-procumbens-exert-anti-asthmatic-effect-via-multitargeting-activity
#14
Jihyun Youm, Hyunyong Lee, Youngwoo Choi, Joobyoung Yoon
Our previous study revealed that the ethanolic extract of Justicia procumbens ameliorates ovalbumin-induced airway inflammation and airway hyper-responsiveness in a mouse model of asthma. However, the mechanism of action of the extract remains unknown. In this study, we prepared DW2008S, an optimized and standardized powder extracted from J. procumbens using anhydrous ethanol, and investigated its anti-asthmatic effect and mechanism of action. Our results showed that DW2008S contains two major ingredients, justicidin A (JA) and justicidin B (JB), which selectively inhibit T helper 2 (Th2) cell responses in concanavalin A-activated spleen cells and polarized Th2 cells...
May 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29484440/importance-of-immune-monitoring-approaches-and-the-use-of-immune-checkpoints-for-the-treatment-of-diffuse-intrinsic-pontine-glioma-from-bench-to-clinic-and-vice-versa-review
#15
Jorge Augusto Borin Scutti
On the basis of immunological results, it is not in doubt that the immune system is able to recognize and eliminate transformed cells. A plethora of studies have investigated the immune system of patients with cancer and how it is prone to immunosuppression, due in part to the decrease in lymphocyte proliferation and cytotoxic activity. The series of experiments published following the demonstration by Dr Allison's group of the potential effect of anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) paved the way for a new perception in cancer immunotherapy: Immune checkpoints...
April 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29440271/phosphorylated-immunoreceptor-tyrosine-based-activation-motifs-and-integrin-cytoplasmic-domains-activate-spleen-tyrosine-kinase-via-distinct-mechanisms
#16
Lina Antenucci, Vesa P Hytönen, Jari Ylänne
Spleen tyrosine kinase (Syk) is involved in cellular adhesion and also in the activation and development of hematopoietic cells. Syk activation induced by genomic rearrangement has been linked to certain T-cell lymphomas, and Syk inhibitors have been shown to prolong survival of patients with B-cell lineage malignancies. Syk is activated either by its interaction with a double-phosphorylated immunoreceptor tyrosine-based activation motif (pITAM), which induces rearrangements in the Syk structure, or by the phosphorylation of specific tyrosine residues...
March 30, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29401630/tetrandrine-attenuates-the-bone-erosion-in-collagen-induced-arthritis-rats-by-inhibiting-osteoclastogenesis-via-spleen-tyrosine-kinase
#17
Yugai Jia, Yumeng Miao, Mengfan Yue, Mei Shu, Zhifeng Wei, Yue Dai
Tetrandrine, a bisbenzylisoquinoline alkaloid, was previously demonstrated to attenuate inflammation and cartilage destruction in the ankles of mice with collagen-induced arthritis (CIA). Here, we explored the underlying mechanism by which tetrandrine prevented arthritis-induced bone erosion by focusing on the differentiation and function of osteoclasts. We found that daily administration of tetrandrine (30 mg/kg) markedly reduced the bone damage and decreased the number of osteoclasts in CIA rats. In vitro, tetrandrine inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis at the early stage and reduced the expressions of osteoclast-related marker genes...
January 30, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29361046/targeted-endothelial-gene-deletion-of-triggering-receptor-expressed-on-myeloid-cells-1-protects-mice-during-septic-shock
#18
Lucie Jolly, Kevin Carrasco, Marc Derive, Jérémie Lemarié, Amir Boufenzer, Sébastien Gibot
AIMS: TREM-1 (Triggering Receptor Expressed on Myeloid cells-1) is an immunoreceptor expressed on neutrophils and monocytes/macrophages whose role is to amplify the inflammatory response driven by Toll-Like Receptors engagement. The pharmacological inhibition of TREM-1 confers protection in several pre-clinical models of acute inflammation. In this study, we aimed to decipher the role of TREM-1 on the endothelium. METHODS AND RESULTS: We first showed by qRT-PCR, flow cytometry and confocal microscopy that TREM-1 was expressed in human pulmonary microvascular endothelial cells as well as in mouse vasculature (aorta, mesenteric artery, and pulmonary vessels)...
January 19, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29349889/t-cell-immunoglobulin-and-itim-domain-contributes-to-cd8-t-cell-immunosenescence
#19
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...
April 2018: Aging Cell
https://www.readbyqxmd.com/read/29345376/role-of-negative-regulation-of-immune-signaling-pathways-in-neutrophil-function
#20
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
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