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https://www.readbyqxmd.com/read/29046437/modulation-of-global-transcriptional-regulatory-networks-as-a-strategy-for-increasing-kanamycin-resistance-of-the-translational-elongation-factor-g-mutants-in-escherichia-coli
#1
Aalap Mogre, Reshma T V, Aswin Sai Narain Seshasayee
Evolve and resequence experiments have provided us a tool to understand bacterial adaptation to antibiotics. In our previous work, we had used short term evolution to isolate mutants resistant to the ribosome targeting antibiotic kanamycin, and reported that Escherichia coli develops low cost resistance to kanamycin via  different point mutations in the translation Elongation Factor-G (EF-G). Furthermore, we had shown that the resistance of EF-G mutants could be increased by second site mutations in the genes rpoD / cpxA / topA / cyaA Mutations in three of these genes had been discovered in earlier screens for aminoglycoside resistance...
October 18, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29045964/-increased-serum-c-c-chemokine-ligand-19-levels-correlated-with-b-cell-abnormalities-in-systemic-lupus-erythematosus
#2
H J Liu, L J Shi, F L Hu, H H Yao, Z G Li, Y Jia
OBJECTIVE: To detect the levels of serum C-C chemokine ligand 19 (CCL19) in patients with systemic lupus erythematosus (SLE) and to evaluate the correlation between CCL19 expression and clinical features and laboratory parameters, trying to reveal the possible role of CCL19 in the pathogenesis of systemic lupus erythematosus. METHODS: The levels of serum CCL19 were measured by enzyme linked immunosorbent assay (ELISA) in 90 patients with SLE and 30 healthy controls...
October 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/29038451/tc-ptp-regulates-the-il-7-transcriptional-response-during-murine-early-t-cell-development
#3
K A Pike, T Hatzihristidis, S Bussières-Marmen, F Robert, N Desai, D Miranda-Saavedra, J Pelletier, M L Tremblay
Cytokines play a critical role in directing the discrete and gradual transcriptional changes that define T cell development. The interleukin-7 receptor (IL-7R), via its activation of the JAK-STAT pathway, promotes gene programs that change dynamically as cells progress through T cell differentiation. The molecular mechanism(s) directing differential gene expression downstream of the IL-7R are not fully elucidated. Here, we have identified T cell protein tyrosine phosphatase (TC-PTP), also known as PTPN2, as a negative regulator of IL-7R-STAT signaling in T cell progenitors, contributing to both the quantitative and qualitative nature of STAT-gene targeting...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29021521/tristetraprolin-inhibits-macrophage-il-27-induced-activation-of-antitumour-cytotoxic-t-cell-responses
#4
Qinghong Wang, Huan Ning, Hui Peng, Lin Wei, Rong Hou, Daniel F Hoft, Jianguo Liu
IFN-γ-producing cytotoxic T lymphocytes are essential for host defense against viral infection and cancer. Here we show that the RNA-binding tristetraprolin, encoded by Zfp36, is needed for CD8(+) T-cell production of IFN-γ in vivo. When activated in vitro, however, IFN-γ production by naive wild type and tristetraprolin-deficient CD8(+) T-cells is comparable. IL-27 is overproduced by tristetraprolin-deficient macrophages and increased systemically in tristetraprolin-deficient mice. Tristetraprolin suppresses IL-27 production by promoting p28 mRNA degradation...
October 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28993778/potential-role-of-v%C3%AE-2-%C3%AE-%C3%AE-t-cells-in-regulation-of-immune-activation-in-primary-hiv-infection
#5
Nupur Bhatnagar, Pierre-Marie Girard, Moises Lopez-Gonzalez, Céline Didier, Lio Collias, Corinne Jung, Diane Bollens, Claudine Duvivier, Cassandre Von Platen, Daniel Scott-Algara, Laurence Weiss
Although conventional regulatory T cells (Tregs) are sufficient in controlling low residual T-cell activation in ART-treated patients, they are not efficient in controlling exaggerated immune activation associated with high levels of HIV replication in primary HIV infection (PHI). Our previous data suggested that double negative (DN) T cells including mainly γδ DN T cells play a role in the control of immune activation in PHI. Since γδ T cells are capable of exerting regulatory functions, we investigated their implication as Tregs in PHI as well as chronic HIV infection (CHI)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28991130/autoimmune-lymphoproliferative-syndrome-masquerading-as-posttransplant-lymphoproliferative-disorder
#6
Sarah M Jeffreys, Rebecca A Levy, Shelley E Crary
We present a case of a 2-year-old female presenting with diffuse lymphadenopathy 2 years following orthotopic heart transplant. Initially, she was diagnosed with posttransplant lymphoproliferative disease based on clinical presentation and pathology and she was treated accordingly. Because of persistent lymphadenopathy following the completion of chemotherapy and new onset of autoimmune cytopenias, repeat flow of the lymph node showed an elevated double negative T-cell population prompting evaluation for autoimmune lymphoproliferative syndrome (ALPS)...
October 4, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28977800/xrcc2-deficient-cells-are-highly-sensitive-to-5-fluorouracil-in-colorectal-cancer
#7
Yong-Zhou Zhang, Ji-Hong An, Yu-Xin Liu, Xian-Chuang Wu, Shan-Shan Han, Xue-Qun Ren, Chang-Jiang Qin
BACKGROUND/AIMS: Inhibition of the repair of 5-fluorouracil (5-FU)-induced DNA lesions may improve the responses of tumors to anticancer agents. XRCC2 is a key factor in DNA repair. However, the role of XRCC2 in the chemoresistance of colorectal cancer (CRC) treated with 5-FU remains unclear. The aim of this study is to investigate whether XRCC2 expression affects the chemosensitivity of colorectal cancer. METHODS: XRCC2 expression in CRC tissues was assessed, and the outcomes were analyzed to determine the clinical importance of XRCC2 expression...
October 5, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28958836/in-vivo-blockade-of-t-cell-development-reveals-alternative-pathways-for-generation-of-intraepithelial-lymphocytes-in-mice
#8
Surenchimeg Mondoon, Kensuke Shibata, Yasunobu Yoshikai
Intraepithelial lymphocytes (IELs) are resident cells localized within the intestinal epithelia and play an important role in regulating gut inflammations and host defense against pathogens. CD8α(+) TCRαβ(+) IELs are heterogeneous populations that are generated from T cell precursors including CD4(-) CD8α(-) double-negative (DN) cells and CD4(+) CD8α(+) double-positive (DP) cells. However, developmental pathways of TCRαβ(+) IELs remained unclear. To gain insight into the mechanisms, we generated mice (Bcl11b(ΔDN2) mice) that lack thymic precursors (DN CD5(+) TCRβ(+) cells) for CD4(-) CD8αα(+) TCRαβ(+) IELs...
November 2017: Immunology Letters
https://www.readbyqxmd.com/read/28956469/alpha-beta-double-negative-t-cells-in-children-with-systemic-lupus-erythematosus-the-relation-to-disease-activity-and-characteristics
#9
Zeinab A El-Sayed, Rasha H El-Owaidy, Neama L Mohamed, Beshoy A Shehata
OBJECTIVES: We aimed to investigate alpha beta double negative (αβ DN) T-cell percentages in juvenile systemic lupus erythematosus (JSLE) and their relation to disease activity and organ involvement. METHODS: This prospective study was carried out over a period of 12 months and included 21 JSLE patients and 20 healthy matched controls. SLE disease activity index 2000 (SLEDAI-2K) scores were recorded in addition to αβ DN T-cell percentages measurement at enrollment and after remission...
September 28, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28951199/a-t-cell-specific-knockout-reveals-an-important-role-for-protease-activated-receptor-2-in-lymphocyte-development
#10
Nidhish Francis, Alison L Every, Babatunde A Ayodele, Robert N Pike, Eleanor J Mackie, Charles N Pagel
Activation of protease-activated receptor-2 (PAR2) expressed by T cells has been linked to the bone loss associated with periodontitis. We generated PAR2 conditional-null mice and crossed these with mice expressing Cre recombinase under control of the Lck proximal promoter, to produce T cell-specific PAR2-null mice in order to further study the cellular mechanism involved in periodontitis. Here we report that efficient deletion of PAR2 in thymocytes isolated from T cell-specific PAR2-null mice resulted in thymic and splenic hypoplasia and a reduction in the cells of the cortex and a loss of distinction between the cortex and the medulla of the thymus...
September 22, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28947542/nur77-regulates-nondeletional-mechanisms-of-tolerance-in-t-cells
#11
Qian Nancy Hu, Alexander Y W Suen, Laura M Henao Caviedes, Troy A Baldwin
Negative selection against highly self-reactive thymocytes is critical for preventing autoimmunity. Thymocyte deletion, anergy induction, and agonist selection are all forms of negative selection that can occur following a high-affinity TCR signal. Of Bim and Nur77, two TCR-induced proteins with proapoptotic function, Bim has been shown to be important for clonal deletion in several model systems, whereas Nur77 was often dispensable. However, Nur77 has been reported to influence other aspects of T cell development by mechanisms that may not be related to its proapoptotic function...
September 25, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28912775/shared-and-distinct-phenotypes-and-functions-of-human-cd161-v%C3%AE-7-2-t-cell-subsets
#12
Ayako Kurioka, Aminu S Jahun, Rachel F Hannaway, Lucy J Walker, Joannah R Fergusson, Eva Sverremark-Ekström, Alexandra J Corbett, James E Ussher, Christian B Willberg, Paul Klenerman
Human mucosal-associated invariant T (MAIT) cells are an important T cell subset that are enriched in tissues and possess potent effector functions. Typically such cells are marked by their expression of Vα7.2-Jα33/Jα20/Jα12 T cell receptors, and functionally they are major histocompatibility complex class I-related protein 1 (MR1)-restricted, responding to bacterially derived riboflavin synthesis intermediates. MAIT cells are contained within the CD161++ Vα7.2+ T cell population, the majority of which express the CD8 receptor (CD8+), while a smaller fraction expresses neither CD8 or CD4 coreceptor (double negative; DN) and a further minority are CD4+...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28894001/intestinal-type-1-regulatory-t-cells-migrate-to-periphery-to-suppress-diabetogenic-t-cells-and-prevent-diabetes-development
#13
Hua Yu, Nicola Gagliani, Harumichi Ishigame, Samuel Huber, Shu Zhu, Enric Esplugues, Kevan C Herold, Li Wen, Richard A Flavell
Growing insight into the pathogenesis of autoimmune diseases and numerous studies in preclinical models highlights the potential of regulatory T cells to restore tolerance. By using non-obese diabetic (NOD) BDC2.5 TCR-transgenic (Tg), and IL-10 and Foxp3 double-reporter mice, we demonstrate that alteration of gut microbiota during cohousing experiments or treatment with anti-CD3 mAb significantly increase intestinal IL-10-producing type 1 regulatory T (Tr1) cells and decrease diabetes incidence. These intestinal antigen-specific Tr1 cells have the ability to migrate to the periphery via a variety of chemokine receptors such as CCR4, CCR5, and CCR7 and to suppress proliferation of Th1 cells in the pancreas...
September 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28892044/a-novel-mouse-model-of-rhabdomyosarcoma-underscores-the-dichotomy-of-mdm2-alt1-function-in-vivo
#14
D F Comiskey, A G Jacob, B L Sanford, M Montes, A K Goodwin, H Steiner, E Matsa, A S Tapia-Santos, T W Bebee, J Grieves, K La Perle, P Boyaka, D S Chandler
Alternative splicing of the oncogene murine double minute 2 (MDM2) is induced in response to genotoxic stress. MDM2-ALT1, the major splice variant generated, is known to activate the p53 pathway and impede full-length MDM2's negative regulation of p53. Despite this perceptible tumor-suppressive role, MDM2-ALT1 is also associated with several cancers. Furthermore, expression of MDM2-ALT1 has been observed in aggressive metastatic disease in pediatric rhabdomyosarcoma (RMS), irrespective of histological subtype...
September 11, 2017: Oncogene
https://www.readbyqxmd.com/read/28878277/increased-tcr-signal-strength-in-dn-thymocytes-promotes-development-of-gut-tcr%C3%AE-%C3%AE-cd8%C3%AE-%C3%AE-intraepithelial-lymphocytes
#15
Capucine L Grandjean, Nital Sumaria, Stefania Martin, Daniel J Pennington
CD4((+))CD8((+)) "double positive" (DP) thymocytes differentiate into diverse αβ T cell sub-types using mechanistically distinct programs. For example, conventional αβ T cells develop from DP cells after partial-agonist T cell receptor (TCR) interactions with self-peptide/MHC, whereas unconventional αβ T cells, such as TCRαβ((+))CD8αα((+)) intraepithelial lymphocytes (IELs), require full-agonist TCR interactions. Despite this, DP cells appear homogeneous, and it remains unclear how distinct TCR signalling instructs distinct developmental outcomes...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28835458/il-2-shapes-the-survival-and-plasticity-of-il-17-producing-%C3%AE-%C3%AE-t-cells
#16
Theresa M Corpuz, Rodrigo Vazquez-Lombardi, Jason K Luong, Joanna Warren, Jessica Stolp, Daniel Christ, Cecile King, Robert Brink, Jonathan Sprent, Kylie E Webster
IL-17-producing γδ T (γδT-17) cells have proved to be an important early source of IL-17 in many inflammatory settings and are emerging as an important participant in protumor immune responses. Considering that their peripheral activation depends largely on innate signals rather than TCR ligation, it is important to understand what mechanisms exist to curb unwanted activation. Expression of the high-affinity IL-2R on γδT-17 cells prompted us to investigate a role for this cytokine. We found γδT-17 cells to be enriched, not depleted, in IL-2-deficient mice...
August 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28833081/transcriptional-repressor-blimp1-regulates-follicular-regulatory-t-cell-homeostasis-and-function
#17
Guang Yang, Xiaosu Yang, Junmei Zhang, Guancheng Li, Dandan Zheng, Anjiao Peng, Jue Hu, Liqun Xu, Baifeng Yang, Huan Yang, Wenbin Zhou, Erdem Tuzun, Jing Li
The B-lymphocyte-induced maturation protein 1 (Blimp1) regulates T-cell homeostasis and function. Loss of Blimp1 could double the proportion of follicular regulatory T (Tfr) cells. However, the effects that Blimp1 may have on the function of Tfr cells remain unknown. Here we document the function for Blimp1 in Tfr cells in vitro and in vivo. Data presented in this study demonstrate that Tfr cells indirectly inhibit the activation and differentiation of B cells by negatively regulating follicular helper T cells, so lowering the secretion of antibody...
August 20, 2017: Immunology
https://www.readbyqxmd.com/read/28822225/altered-thymocyte-and-t-cell-development-in-neonatal-mice-with-hyperoxia-induced-lung-injury
#18
Sowmya Angusamy, Tamer Mansour, Mohammed Abdulmageed, Rachel Han, Brian C Schutte, John LaPres, Jack R Harkema, Said A Omar
BACKGROUND: The adaptive immune system of neonates is relatively underdeveloped. The thymus is an essential organ for adaptive T cell development and might be affected during the natural course of oxygen induced lung injury. The effect of prolonged hyperoxia on the thymus, thymocyte and T cell development, and its proliferation has not been studied extensively. METHODS: Neonatal mice were exposed to 85% oxygen (hyperoxia) or room air (normoxia) up to 28 days. Flow cytometry using surface markers were used to assay for thymocyte development and proliferation...
August 19, 2017: Journal of Perinatal Medicine
https://www.readbyqxmd.com/read/28817603/expression-of-the-mhc-class-ii-in-triple-negative-breast-cancer-is-associated-with-tumor-infiltrating-lymphocytes-and-interferon-signaling
#19
In Ah Park, Seong-Hye Hwang, In Hye Song, Sun-Hee Heo, Young-Ae Kim, Won Seon Bang, Hye Seon Park, Miseon Lee, Gyungyub Gong, Hee Jin Lee
Tumor-infiltrating lymphocytes (TILs) have been known for their strong prognostic and predictive significance in triple-negative breast cancer (TNBC). Several mechanisms for TIL influx in TNBC have been elucidated. Major histocompatibility complex class II (MHC-II) is an essential component of the adaptive immune system and is generally restricted to the surface of antigen-presenting cells. However, it has been reported that interferon-gamma signaling may induce MHC-II in almost all cell types, including those derived from cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28777210/rapamycin-prolongs-graft-survival-and-induces-cd4-ifn-%C3%AE-il-10-regulatory-type-1-cells-in-old-recipient-mice
#20
Markus Quante, Timm Heinbokel, Karoline Edtinger, Koichiro Minami, Hirofumi Uehara, Yeqi Nian, Haruhito Azuma, Reza Abdi, Abdallah Elkhal, Stefan G Tullius
BACKGROUND: Although the elderly represents a rapidly growing population among transplant recipients, age-specific aspects have not been considered sufficiently in clinical trials. Moreover, age-specific effects of immunosuppressive therapies remain poorly understood. METHODS: Here, we assessed the impact of Rapamycin on alloimmune responses in old recipients using a fully MHC-mismatched murine transplantation model. RESULTS: Old untreated recipients displayed a prolonged skin graft survival compared to their young counterparts, an observation that confirmed data of our previous experiments...
August 2, 2017: Transplantation
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