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https://www.readbyqxmd.com/read/28818640/the-influence-of-physical-activity-in-the-anti-tumor-immune-response-in-experimental-breast-tumor
#1
Thiago M Bianco, Douglas R Abdalla, Chamberttan S Desidério, Sofie Thys, Cindy Simoens, John-Paul Bogers, Eddie F C Murta, Márcia A Michelin
This study aimed to investigate the influence of physical activity in innate immunity to conduce to an effective antitumoral immune response analyzing the phenotype and activation status of infiltrating cells. We analyzed the intracellular cytokines and the transcription factors of tumor infiltrating lymphocytes (TILS) and spleen leukocytes. The Nos2 gene expression was evaluated in spleen cells and futhermore the ROS production was measured and spleen cells; another cell evaluated was dendritic cells (TIDCs), their cytokines expression and membrane molecules; finally to understood the results obtained, we analysed the dendritic cells obtained from bone marrow...
August 14, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28815219/conventional-nk-cells-and-ilc1-are-partially-ablated-in-the-livers-of-ncr1-icre-tbx21-fl-fl-mice
#2
Antonia O Cuff, Victoria Male
Mouse liver contains both Eomes-dependent conventional natural killer (cNK) cells and Tbet-dependent liver-resident type I innate lymphoid cells (ILC1). In order to better understand the role of ILC1, we attempted to generate mice that would lack liver ILC1, while retaining cNK, by conditional deletion of Tbet in NKp46+ cells. Here we report that the Ncr1 (iCre)Tbx21 (fl/fl) mouse has a roughly equivalent reduction in both the cNK and ILC1 compartments of the liver, limiting its utility for investigating the relative contributions of these two cell types in disease models...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28780965/regulation-of-systemic-autoimmunity-and-cd11c-tbet-b-cells-by-swef-proteins
#3
Michela Manni, Edd Ricker, Alessandra B Pernis
Recent studies have revealed the existence of a T-bet dependent subset of B cells, which expresses unique phenotypic and functional characteristics including high levels of CD11c and CD11b. In the murine system this B cell subset has been termed Age/autoimmune-associated B cells (ABCs) since it expands with age in non-autoimmune mice and it prematurely accumulates in autoimmune-prone strains. The molecular mechanisms that promote the expansion and function of ABCs are largely unknown. This review will focus on the SWEF proteins, a small family of Rho GEFs comprised of SWAP-70 and its homolog DEF6, a newly identified risk variant for human SLE...
July 11, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28765611/the-differentiation-of-ror-%C3%AE-t-expressing-inkt17-cells-is-orchestrated-by-runx1
#4
Puspa Thapa, Bryce Manso, Ji Young Chung, Sinibaldo Romera Arocha, Hai-Hui Xue, Derek B Sant' Angelo, Virginia Smith Shapiro
iNKT cells are a unique lineage of T cells that recognize glycolipid presented by CD1d. In the thymus, they differentiate into iNKT1, iNKT2 and iNKT17 effector subsets, characterized by preferential expression of Tbet, Gata3 and ROR-γt and production of IFN-γ, IL-4 and IL-17, respectively. We demonstrate that the transcriptional regulator Runx1 is essential for the generation of ROR-γt expressing iNKT17 cells. PLZF-cre Runx1 cKO mice lack iNKT17 cells in the thymus, spleen and liver. Runx1-deficient iNKT cells have altered expression of several genes important for iNKT17 differentiation, including decreased expression of IL-7Rα, BATF and c-Maf and increased expression of Bcl11b and Lef1...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28756630/dna-methylation-of-th2-lineage-determination-genes-at-birth-is-associated-with-allergic-outcomes-in-childhood
#5
Sheila Barton, Sherry Ngo, Paula Costello, Emma Garratt, Sarah El-Heis, Elie Antoun, Rebecca Clarke-Harris, Robert Murray, Tejal Bhatt, Graham Burdge, Cyrus Cooper, Hazel Inskip, Eline M van der Beek, Allan Sheppard, Keith M Godfrey, Karen A Lillycrop
BACKGROUND: There is now increasing evidence that asthma and atopy originate in part in utero, with disease risk being associated with the altered epigenetic regulation of genes. OBJECTIVE AND METHODS: To determine the relationship between variations in DNA methylation at birth and the development of allergic disease, we examined the methylation status of CpG loci within the promoter regions of Th1/2 lineage commitment genes (GATA3, IL-4, IL-4R, STAT4 and TBET) in umbilical cord DNA at birth in a cohort of infants from the Southampton Women's Survey (n=696) who were later assessed for asthma, atopic eczema and atopy...
July 30, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28750779/pro-inflammatory-dual-receptor-t-cells-in-chronic-graft-versus-host-disease
#6
Amritha Balakrishnan, Nicholas Gloude, Roman Sasik, Edward D Ball, Gerald P Morris
Defective post-transplant thymopoiesis is associated with chronic graft versus host disease (cGVHD), a multi-organ pathology affecting up to 80% of patients following allogeneic hematopoietic stem cell transplantation (HSCT). Previous work demonstrated that the subset of T cells expressing two T cell receptors (TCRs) is predisposed to alloreactivity, driving selective and disproportionate activity in acute GVHD in both mouse models and HSCT patients. Here we investigate a potential role for this pathogenic T cell subset in cGVHD...
July 24, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28680760/tbet-and-il-36%C3%AE-cooperate-in-therapeutic-dc-mediated-promotion-of-ectopic-lymphoid-organogenesis-in-the-tumor-microenvironment
#7
Aliyah M Weinstein, Lu Chen, Emily A Brzana, Prashanti R Patil, Jennifer L Taylor, Kellsye L Fabian, Callen T Wallace, Sabrina D Jones, Simon C Watkins, Binfeng Lu, David F Stroncek, Timothy L Denning, Yang-Xin Fu, Peter A Cohen, Walter J Storkus
We have previously reported that direct injection of dendritic cells (DC) engineered to express the Type-1 transactivator Tbet (i.e., DC.Tbet) into murine tumors results in antitumor efficacy in association with the development of structures resembling tertiary lymphoid organs (TLO) in the tumor microenvironment (TME). These TLO contained robust infiltrates of B cells, DC, NK cells, and T cells in proximity to PNAd(+) blood vessels; however, they were considered incomplete, since the recruited B cells failed to organize into classic germinal center-like structures...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28615417/t-cell-restricted-notch-signaling-contributes-to-pulmonary-th1-and-th2-immunity-during-cryptococcus-neoformans-infection
#8
Lori M Neal, Yafeng Qiu, Jooho Chung, Enze Xing, Woosung Cho, Antoni N Malachowski, Ashley R Sandy-Sloat, John J Osterholzer, Ivan Maillard, Michal A Olszewski
Cryptococcus neoformans is a ubiquitous, opportunistic fungal pathogen but the cell signaling pathways that drive T cell responses regulating antifungal immunity are incompletely understood. Notch is a key signaling pathway regulating T cell development, and differentiation and functional responses of mature T cells in the periphery. The targeting of Notch signaling within T cells has been proposed as a potential treatment for alloimmune and autoimmune disorders, but it is unknown whether disturbances to T cell immunity may render these patients vulnerable to fungal infections...
July 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28610780/analysis-of-transcription-factors-micrornas-and-cytokines-involved-in-t-lymphocyte-differentiation-in-patients-with-tuberculosis-after-directly-observed-treatment-short-course
#9
Nancy Elizabeth Corral-Fernández, Juan Diego Cortes-García, Rivas-Santiago Bruno, Silvia Romano-Moreno, Susanna E Medellín-Garibay, Martín Magaña-Aquino, Raúl A Salazar-González, Roberto González-Amaro, Diana Patricia Portales-Pérez
Tuberculosis (Tb) is an infectious disease in which the immune system plays an important role. MicroRNAs are involved in the development and maintenance of CD4 + T lymphocyte subpopulations. miR-326 regulates the differentiation to Th17 cells and miR-29 correlates with the Th1 response. The aim of this study was to determine the role of microRNAs, Transcription Factors, and cytokines in Th differentiation before and after the directly observed treatment short-course (DOTS). Peripheral blood mononuclear cells and serum from Tb patients were collected at times 0 (before therapy), 2 (after the intensive phase), and 6 months (after the holding phase)...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28584007/t-cell-derived-il-10-impairs-host-resistance-to-mycobacterium-tuberculosis-infection
#10
Lúcia Moreira-Teixeira, Paul S Redford, Evangelos Stavropoulos, Nico Ghilardi, Craig L Maynard, Casey T Weaver, Ana Paula Freitas do Rosário, Xuemei Wu, Jean Langhorne, Anne O'Garra
Tuberculosis (TB), caused by Mycobacterium tuberculosis infection, is a leading cause of mortality and morbidity, causing ∼1.5 million deaths annually. CD4(+) T cells and several cytokines, such as the Th1 cytokine IFN-γ, are critical in the control of this infection. Conversely, the immunosuppressive cytokine IL-10 has been shown to dampen Th1 cell responses to M. tuberculosis infection impairing bacterial clearance. However, the critical cellular source of IL-10 during M. tuberculosis infection is still unknown...
July 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28572155/elastin-receptor-s-gal-occupancy-by-elastin-peptides-modulates-t-cell-response-during-murine-emphysema
#11
Aïda Meghraoui-Kheddar, Alexandre Pierre, Mehdi Sellami, Sandra Audonnet, Flora Lemaire, Richard Le Naour
Chronic obstructive pulmonary disease and emphysema are associated with increased elastin peptides (EP) production due to excessive breakdown of lung connective tissue. We recently reported that exposure of mice to EP elicited hallmark features of emphysema. EP effects are largely mediated through a receptor complex which includes the elastin-binding protein S-gal. In previous studies, we established a correlation between cytokine production and S-gal protein expression in EP treated immune cells. In this study, we investigated the S-gal-dependent EP effects on T helper (Th) and T cytotoxic (Tc) responses during murine EP-triggered pulmonary inflammation...
June 1, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28567040/a-unique-cellular-and-molecular-microenvironment-is-present-in-tertiary-lymphoid-organs-of-patients-with-spontaneous-prostate-cancer-regression
#12
María de la Luz García-Hernández, Norma Ofelia Uribe-Uribe, Ricardo Espinosa-González, W Martin Kast, Shabaana A Khader, Javier Rangel-Moreno
OBJECTIVE: Multiple solid cancers contain tertiary lymphoid organs (TLO). However, it is unclear whether they promote tumor rejection, facilitate tumor evasion, or simply whether they are a byproduct of chronic inflammation. We hypothesize that although chronic inflammation induces TLO formation, the tumor milieu can modulate TLO organization and functions in prostate cancer. Therefore, our study seeks to elucidate the cellular and molecular signatures in unique prostatectomy specimens from evanescent carcinoma patients to identify markers of cancer regression, which could be harnessed to modulate local immunosuppression or potentially enhance TLO function...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28550044/t-cells-lacking-hdac11-have-increased-effector-functions-and-mediate-enhanced-alloreactivity-in-a-murine-model
#13
David M Woods, Karrune V Woan, Fengdong Cheng, Andressa L Sodré, Dapeng Wang, Yongxia Wu, Zi Wang, Jie Chen, John Powers, Javier Pinilla-Ibarz, Yu Yu, Ya Zhang, Xuefeng Wu, Xiaoyan Zheng, Jeffrey Weber, Wayne W Hancock, Edward Seto, Alejandro Villagra, Xue-Zhong Yu, Eduardo M Sotomayor
Histone acetylation and the families of enzymes responsible for controlling these epigenetic marks have been implicated in regulating T-cell maturation and phenotype. Here, we demonstrate a previously undefined role of histone deacetylase 11 (HDAC11) in regulating T-cell effector functions. Using EGFP-HDAC11 transgenic reporter mice, we found that HDAC11 expression was lower in effector relative to naive and central memory T-cell populations, and activation of resting T cells resulted in its decreased expression...
July 13, 2017: Blood
https://www.readbyqxmd.com/read/28521792/m2-macrophage-is-the-predominant-phenotype-in-airways-inflammatory-lesions-in-patients-with-granulomatosis-with-polyangiitis
#14
Alexandre Wagner Silva de Souza, Mirjan van Timmeren, Jan-Stephan Sanders, Coen Stegeman, Peter Heeringa, Cees G M Kallenberg, Johanna Westra
BACKGROUND: Macrophages may present two distinct phenotypes indicated as M1 and M2 under different stimuli. M1 and M2 macrophages have divergent functions that range from enhancement of inflammation for M1 to tissue repair and remodeling for M2 macrophages. The objective of this study was to evaluate the distribution of M1 and M2 macrophage phenotypes in biopsies from the airways of patients with active granulomatosis with polyangiitis (GPA) and to analyze their associations with T and B cells in those biopsies, and with nasal carriage of Staphylococcus aureus, disease parameters and therapy...
May 18, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28485520/murine-thymic-nk-cells-a-case-of-identity
#15
Victoria Male, Hugh J M Brady
Just over a decade ago, it was established that NK cells in the thymus do not follow precisely the same developmental pathway as conventional NK cells that develop in the bone marrow. Subsequently, it has emerged that NK cells are one branch of a family of innate lymphoid cells (ILCs). ILC1s and thymic NK cells have, however, sufficient similarities such that questions have been raised about how distinctive each cell type is from the other. In this issue of European Journal of Immunology, Gabrielli et al. [Eur...
May 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28473623/tbet-is-a-critical-modulator-of-foxp3-expression-in-autoimmune-graft-versus-host-disease
#16
Shoba Amarnath, Arian Laurence, Nathaniel Zhu, Renato Cunha, Michael A Eckhaus, Samuel Taylor, Jason E Foley, Monalisa Ghosh, Tania C Felizardo, Daniel H Fowler
CD4(+) T-helper subsets drive autoimmune chronic graft-versus-host disease, a major complication after allogeneic bone marrow transplantation. However, it remains unclear how specific T-helper subsets contribute to chronic graft-versus-host disease. T-helper type 1 cells are one of the major disease-mediating T-cell subsets and require interferon-γ signaling and Tbet expression for their function. Regulatory T cells on the other hand can inhibit T-helper type 1 cell-mediated responses. Using an established murine model that isolates the autoimmune component of graft-versus-host disease, we hypothesized that T-helper type 1 cells would restrict FoxP3-driven regulatory T cells...
August 2017: Haematologica
https://www.readbyqxmd.com/read/28451323/aiegens-for-dark-through-bond-energy-transfer-design-synthesis-theoretical-study-and-application-in-ratiometric-hg-2-sensing
#17
Yuncong Chen, Weijie Zhang, Yuanjing Cai, Ryan T K Kwok, Yubing Hu, Jacky W Y Lam, Xinggui Gu, Zikai He, Zheng Zhao, Xiaoyan Zheng, Bin Chen, Chen Gui, Ben Zhong Tang
A novel dark through-bond energy transfer (DTBET) strategy is proposed and applied as the design strategy to develop ratiometric Hg(2+) sensors with high performance. Tetraphenylethene (TPE) derivatives with aggregation-induced emission (AIE) characteristics are selected as dark donors to eliminate emission leakage from the donors. The TBET mechanism has been adopted since it experiences less influence from spectral overlapping than Förster resonance energy transfer (FRET), making it more flexible for developing cassettes with large pseudo-Stokes shifts...
March 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28412624/effects-of-1-25-dihydroxyvitamin-d3-in-an-ovalbumin-induced-allergic-rhinitis-model
#18
Baiwen Chen, Shenhong Qu, Min Li, Linsong Ye, Shaojie Zhang, Taijie Qin, Hua Fan
IL-17-producing Th17 cells play an important role in allergic airway diseases, but their local expression and regulation in allergic rhinitis (AR) is not well understood. This study investigated the effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on T-bet expression, Th1 cells, Th2 cells, Th17 cells and IL-33-positive epithelial cells in AR. C57BL/6 mice were intranasally sensitized and challenged with ovalbumin (OVA), and 1,25-(OH)2D3 was intraperitoneally injected into AR mice. Cytokine levels were measured with enzyme-linked immunosorbent assays, phenotypic analysis of Th1, Th2 and Th17 cells in the spleen was completed with flow cytometry, and the CD4(+)IL-17(+) cells in the Nasopharynx-associated lymphoid tissue (NALT) and IL-33-positive cells in nasal mucosa was evaluated with immunofluorescence microscopy...
April 13, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28406139/t-bet-independent-development-of-ifn%C3%AE-secreting-natural-t-helper-1-cell-population-in-the-absence-of-itk
#19
Arun K Kannan, Sonia Mohinta, Weishan Huang, Lu Huang, Nicholas Koylass, Judith A Appleton, Avery August
Th1, Th2, Th9 and Th17 cells are conventional CD4(+) effector T cells identified as secretors of prototypical cytokines IFNγ, IL4, IL9, and IL-17A respectively. Recently, populations of natural Th17 and Th1 cells (nTh17 and nTh1) with innate-like phenotype have been identified in the thymus that are distinct from conventional Th17 and Th1 cells. The absence of the Tec family kinase Interleukin-2 inducible T cell kinase (Itk) results in T cell immunodeficiency in mice and humans. Here we show that Itk negatively regulates the development of nTh1 cells that express IFNγ in a Tbet independent manner, and whose expansion can be enhanced by IL4...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28276053/murine-thymic-nk-cells-are-distinct-from-ilc1s-and-have-unique-transcription-factor-requirements
#20
Sara Gabrielli, Mengxi Sun, April Bell, Erin C Zook, Renee F de Pooter, Loris Zamai, Barbara L Kee
Group 1 innate lymphoid cells include natural killer (NK) cells and ILC1s, which mediate the response to intracellular pathogens. Thymic NK (tNK) cells were described with hybrid features of immature NK cells and ILC1 but whether these cells are related to NK cells or ILC1 has not been fully investigated. We report that murine tNK cells expressed the NK-cell associated transcription factor EOMES and developed independent of the essential ILC1 factor TBET, confirming their placement within the NK lineage. Moreover, tNK cells resemble NK cells rather than ILC1 in their requirements for the E protein transcription factor inhibitor ID2...
May 2017: European Journal of Immunology
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