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https://www.readbyqxmd.com/read/28973925/foxo1-opposition-of-cd8-t-cell-effector-programming-confers-early-memory-properties-and-phenotypic-diversity
#1
Arnaud Delpoux, Chen-Yen Lai, Stephen M Hedrick, Andrew L Doedens
The factors and steps controlling postinfection CD8(+) T cell terminal effector versus memory differentiation are incompletely understood. Whereas we found that naive TCF7 (alias "Tcf-1") expression is FOXO1 independent, early postinfection we report bimodal, FOXO1-dependent expression of the memory-essential transcription factor TCF7 in pathogen-specific CD8(+) T cells. We determined the early postinfection TCF7(high) population is marked by low TIM3 expression and bears memory signature hallmarks before the appearance of established memory precursor marker CD127 (IL-7R)...
October 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28945272/cd4-t-helper-cells-and-regulatory-t-cells-in-active-lupus-nephritis-an-imbalance-towards-a-predominant-th1-response
#2
D Mesquita, G Mastroianni Kirsztajn, M F Franco, L A Reis, S F Perazzio, F V Mesquita, V da Silva Ferreira, L E Coelho Andrade, A W Silva de Souza
The objective of this study was to evaluate the frequency of CD4(+) T cell subsets in peripheral blood mononuclear cells (PBMC), urine and renal tissue from patients with lupus nephritis (LN). PBMC and urinary cells were collected from 17 patients with active LN, 20 disease controls (DC) with primary glomerulonephritis and 10 healthy controls (HC) and were analysed by flow cytometry with markers for T helper type 1 (Th1), Th2, Th17 and regulatory T cells (Treg ) cells. T cell subsets were assessed by immunohistochemistry from LN biopsy specimens from 12 LN patients...
September 25, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28882699/neutrophil-infiltration-is-a-favorable-prognostic-factor-in-early-stages-of-colon-cancer
#3
Maria L Wikberg, Agnes Ling, Xingru Li, Åke Öberg, Sofia Edin, Richard Palmqvist
The tumor immune response has been proven critical to prognosis in colorectal cancer (CRC), but studies on the prognostic role of neutrophil infiltration have shown contradictory results. The aim of this study was to elucidate the prognostic role of infiltrating neutrophils at different intratumoral subsites and in different molecular subgroups of CRC. The relations between neutrophil infiltration and infiltration of other immune cells (T-cell and macrophage subsets) were also addressed. Expression of the neutrophil marker CD66b was assessed by immunohistochemistry in 448 archival human tumor tissue samples from patients surgically resected for CRC...
September 4, 2017: Human Pathology
https://www.readbyqxmd.com/read/28833201/dynamics-of-regulatory-t-cells-tregs-in-patients-with-oral-squamous-cell-carcinoma
#4
Sadhna Aggarwal, Suresh C Sharma, Satya N Das
BACKGROUND AND OBJECTIVES: The immune dysfunction in oral squamous cell carcinoma (OSCC) patients is one of the major factors for growth and dissemination of tumor affecting disease-free survival. METHODS: The phenotypic and functional characteristics of Regulatory T (Treg ) CD4(+) CD25(+) FoxP3(+) subsets in OSCC patients were assessed by multicolor flow cytometry and its effector component (TGF-β) by Western blot and qRT-PCR. RESULTS: An increased (P < 0...
August 22, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28818640/the-influence-of-physical-activity-in-the-anti-tumor-immune-response-in-experimental-breast-tumor
#5
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 analysed 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
#6
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
#7
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
#8
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
#9
S J Barton, S Ngo, P Costello, E Garratt, S El-Heis, E Antoun, R Clarke-Harris, R Murray, T Bhatt, G Burdge, C Cooper, H Inskip, E M van der Beek, A Sheppard, K M Godfrey, K 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/proinflammatory-dual-receptor-t-cells-in-chronic-graft-versus-host-disease
#10
Amritha Balakrishnan, Nicholas Gloude, Roman Sasik, Edward D Ball, Gerald P Morris
Defective post-transplantation thymopoiesis is associated with chronic graft-versus-host disease (GVHD), a multiorgan pathology affecting up to 80% of patients after allogeneic hematopoietic stem cell transplantation (HSCT). Previous work demonstrated that the subset of T cells expressing 2 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 chronic GVHD (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
#11
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
#12
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
#13
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
#14
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
#15
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 because of 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 that includes the elastin-binding protein spliced-galactosidase (S-gal). In previous studies, we established a correlation between cytokine production and S-gal protein expression in EP-treated immune cells...
September 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
#16
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
#17
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
#18
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
#19
COMMENT
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
#20
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
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