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https://www.readbyqxmd.com/read/28550203/socs1-is-a-key-molecule-that-prevents-regulatory-t-cell-plasticity-under-inflammatory-conditions
#1
Reiko Takahashi, Hiroko Nakatsukasa, Shunichi Shiozawa, Akihiko Yoshimura
We previously showed that regulatory T cells (Tregs) from T cell-specific Socs1-deficient mice (Socs1(fl/fl)Lck-Cre(+) mice) easily convert into Th1- or Th17-like cells (ex-Tregs), which lose Foxp3 expression and suppressive functions in vivo. Because Tregs in Socs1(fl/fl)Lck-Cre(+) mice are constantly exposed to a large amount of inflammatory cytokines produced by non-Tregs in vivo, in this study we analyzed Treg-specific Socs1-deficient mice (Socs1(fl/fl)Foxp3(YFP-Cre) mice). These mice developed dermatitis, splenomegaly, and lymphadenopathy that were much milder than those in Socs1(fl/fl)Lck-Cre(+) mice...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28549917/dendritic-cell-derived-exosomes-elicit-tumor-regression-in-autochthonous-hepatocellular-carcinoma-mouse-models
#2
Zhen Lu, Bingfeng Zuo, Renwei Jing, Xianjun Gao, Quan Rao, Zhili Liu, Han Qi, Hongxing Guo, HaiFang Yin
BACKGROUND & AIMS: Dendritic cell (DC)-derived exosomes (DEXs) form a new class of vaccines for cancer immunotherapy. However their potency in hepatocellular carcinoma (HCC), a life-threatening malignancy with limited treatment options in the clinic and responds poorly to immunotherapy, remains to be investigated. METHODS: Exosomes derived from α-fetoprotein (AFP) - expressing DCs (DEXAFP) were investigated in three different HCC mouse models systemically and tumor growth and microenvironment were monitored...
May 23, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28548891/immunological-characteristics-of-colitis-associated-with-anti-ctla-4-antibody-therapy
#3
Giorgos Bamias, Ioanna Delladetsima, Marina Perdiki, Spyros I Siakavellas, Dimitrios Goukos, George V Papatheodoridis, George L Daikos, Helen Gogas
Anti-CTL4-A therapy is associated with development of colitis. We characterized ipilimumab-associated colitis in nine melanoma patients (6 male, mean age: 55.3-yrs). Median value for diarrhea grade was 2, number of ipilimumab doses 2, and interval since last administration 3-wks. Endoscopic characteristics resembled inflammatory bowel disease and histology revealed predominance of plasmacytes or CD4+ T-cells. We observed significant upregulation of Th1 and Th17 effector pathways (>10-fold increase for IFN-γmRNA, >5-fold for IL-17A, p < 0...
May 26, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28545241/lactobacillus-rhamnosus-hn001-and-lactobacillus-acidophilus-la-14-attenuate-gardnerella-vaginalis-infected-bacterial-vaginosis-in-mice
#4
Se-Eun Jang, Jin-Ju Jeong, Su-Young Choi, Hyunji Kim, Myung Joo Han, Dong-Hyun Kim
Oral administration of a probiotic mixture (PM; Respecta(®)) consisting of Lactobacillus rhamnosus HN001 (L1), Lactobacillus acidophilus La-14 (L2), and lactoferrin RCXTM results in colonization of these probiotics in the vagina of healthy women. Therefore, we examined whether vaginal colonization of the PM ingredients L1 and L2 could attenuate bacterial vaginosis (BV). BV was induced in mice via β-estradiol-3-benzoate-induced immunosuppression and intravaginal inoculation with Gardnerella vaginalis (GV)...
May 23, 2017: Nutrients
https://www.readbyqxmd.com/read/28543977/abnormal-ratio-of-cd57-cells-to-cd56-cells-in-women-with-recurrent-implantation-failure
#5
Ruiwei Jiang, Guijun Yan, Jun Xing, Zhilong Wang, Yong Liu, Hongyan Wu, Xiangshan Fan, Jianjun Zhou, Lijun Ding, Haixiang Sun
PROBLEM: To define a more precise parameter for a better understanding of natural killer (NK) cells and its relation with regulatory T cells (Tregs) in women with recurrent implantation failure (RIF). METHOD OF STUDY: The percentages of CD56+ cells, CD57+ cells and Foxp3+ cells in the endometrium and blood from 23 normal controls and 32 women with RIF were measured by immunocytochemistry and flow cytometry. RESULTS: Women with RIF had significantly increased ratio of CD57+ cells to CD56+ cells in both the endometrium (P<...
May 20, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28543436/prenatal-environmental-tobacco-smoke-exposure-increases-allergic-asthma-risk-with-methylation-changes-in-mice
#6
Sonja Christensen, Zeina Jaffar, Elizabeth Cole, Virginia Porter, Maria Ferrini, Britten Postma, Kent E Pinkerton, Mihi Yang, Yang Jee Kim, Luke Montrose, Kevan Roberts, Andrij Holian, Yoon Hee Cho
Allergic asthma remains an inadequately understood disease. In utero exposure to environmental tobacco smoke (ETS) has been identified as an environmental exposure that can increase an individual's asthma risk. To improve our understanding of asthma onset and development, we examined the effect of in utero ETS exposure on allergic disease susceptibility in an asthmatic phenotype using a house dust mite (HDM) allergen-induced murine model. Pregnant C57BL/6 mice were exposed to either filtered air or ETS during gestation, and their offspring were further exposed to HDM at 6-7 weeks old to induce allergic inflammation...
May 25, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28542701/two-separate-effects-contribute-to-regulatory-t-cell-defect-in-sle-patients-and-their-unaffected-relatives
#7
Nuno Costa, Oriana Marques, Sandra I Godinho, Cláudia Carvalho, Barbara Leal, Ana M Figueiredo, Carlos Vasconcelos, António Marinho, Maria F Moraes-Fontes, António Gomes da Costa, Cristina Ponte, Raquel Campanilho-Marques, Telma Cóias, Ana R Martins, João F Viana, Margarida Lima, Berta Martins, Constantin Fesel
FOXP3(+) regulatory T-cells (Tregs) are functionally deficient in Systemic Lupus Erythematosus (SLE), characterized by reduced surface CD25 (the IL-2 receptor alpha chain). Low-dose IL-2 therapy is a promising current approach to correct this defect. To elucidate the origins of the SLE Treg phenotype, we studied its role through developmentally defined Treg subsets in 45 SLE patients, 103 SLE-unaffected first-degree relatives and 61 unrelated healthy control subjects, and genetic association with the CD25-encoding IL2RA locus...
May 24, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28542613/suppression-of-il-12p70-formation-by-il-2-or-following-macrophage-depletion-causes-t-cell-autoreactivity-leading-to-cns-demyelination-in-hsv-1-infected-mice
#8
Dhong Hyun Lee, Mandana Zandian, Jane Kuo, Kevin R Mott, Shuang Chen, Moshe Arditi, Homayon Ghiasi
We have established two mouse models of central nervous system (CNS) demyelination that differ from most other available models of multiple sclerosis (MS) in that they represent a mixture of viral and immune triggers. In the first model, ocular infection of different strains of mice with a recombinant HSV-1 that expresses murine IL-2 constitutively (HSV-IL-2) causes CNS demyelination. In the second model, depletion of macrophages causes CNS demyelination in mice that are ocularly infected with wild-type (WT) HSV-1...
May 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28541302/the-long-noncoding-rna-lnc-egfr-stimulates-t-regulatory-cells-differentiation-thus-promoting-hepatocellular-carcinoma-immune-evasion
#9
Runqiu Jiang, Junwei Tang, Yun Chen, Lei Deng, Jie Ji, Yu Xie, Ke Wang, Wei Jia, Wen-Ming Chu, Beicheng Sun
Long noncoding RNAs play a pivotal role in T-helper cell development but little is known about their roles in Treg differentiation and functions during the progression of hepatocellular carcinoma (HCC). Here, we show that lnc-epidermal growth factor receptor (EGFR) upregulation in Tregs correlates positively with the tumour size and expression of EGFR/Foxp3, but negatively with IFN-γ expression in patients and xenografted mouse models. Lnc-EGFR stimulates Treg differentiation, suppresses CTL activity and promotes HCC growth in an EGFR-dependent manner...
May 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28541089/decreased-frequency-of-peripheral-blood-cd8-cd25-foxp3-regulatory-t-cells-correlates-with-il-33-levels-in-pre-eclampsia
#10
Jianxiu Yu, Lei Qian, Fenghui Wu, Ming Li, Wei Chen, Hongyou Wang
OBJECTIVE: We aimed to investigate the role of CD8(+)CD25(+)Foxp3(+)regulatory T (Treg) cells in pre-eclampsia (PE). METHODS: This was a cross-sectional study of 46 patients with PE and 24 normotensive women within the third trimester of gestation. We analyzed the percentages of CD8(+)CD25(+)Foxp3(+)Treg cells in peripheral blood using flow cytometry and the serum levels of interleukin (IL)-6, IL-17A, IL-10, TGF-β1, IL-1β, and IL-33 by Luminex 200. RESULTS: We found that patients with PE had lower percentages of CD8(+)CD25(+)Foxp3(+)Treg cells than normotensive pregnant women...
May 25, 2017: Hypertension in Pregnancy
https://www.readbyqxmd.com/read/28540823/the-effects-of-hyperthermia-on-the-immunomodulatory-properties-of-human-umbilical-cord-vein-mesenchymal-stem-cells-mscs
#11
Shilan Hesami, Mehdi Mohammadi, Mohamad Ali Rezaee, Ali Jalili, Mohammad Reza Rahmani
PURPOSE: Hyperthermia can modulate inflammation and the immune response. Based on the recruitment of mesenchymal stem cells (MSCs) to inflamed tissues and the immunomodulatory properties of these cells, the aim of this study was to examine the effects of hyperthermia on the immunomodulatory properties of MSCs in a mixed lymphocyte reaction (MLR). MATERIALS AND METHODS: Passages 4-6 of human umbilical cord vein mesenchymal stem cells were co-cultured in a two-way MLR...
May 19, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28540653/il-2-and-il-15-dependent-thymic-development-of-foxp3-expressing-regulatory-t-lymphocytes
#12
REVIEW
Cécile Apert, Paola Romagnoli, Joost P M van Meerwijk
Immunosuppressive regulatory T lymphocytes (Treg) expressing the transcription factor Foxp3 play a vital role in the maintenance of tolerance of the immune-system to self and innocuous non-self. Most Treg that are critical for the maintenance of tolerance to self, develop as an independent T-cell lineage from common T cell precursors in the thymus. In this organ, their differentiation requires signals from the T cell receptor for antigen, from co-stimulatory molecules, as well as from cytokine-receptors. Here we focus on the cytokines implicated in thymic development of Treg, with a particular emphasis on the roles of interleukin-2 (IL-2) and IL-15...
May 24, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28540499/cell-based-therapies-with-t-regulatory-cells
#13
REVIEW
Mateusz Gliwiński, Dorota Iwaszkiewicz-Grześ, Piotr Trzonkowski
CD4(+)CD25(high)FoxP3(+) T regulatory cells (Tregs) are immunodominant suppressors in the immune system. Tregs use various mechanisms to control immune responses. Preclinical data from animal models have confirmed the huge therapeutic potential of Tregs in many immune-mediated diseases. Hence, these cells are now on the road to translation to cell therapy in the clinic as the first clinical trials are accomplished. To date, clinical research has involved mainly hematopoietic stem cell transplantations, solid organ transplantations, and autoimmunity...
May 24, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28539588/cooperation-of-oncolytic-herpes-virotherapy-and-pd-1-blockade-in-murine-rhabdomyosarcoma-models
#14
Chun-Yu Chen, Pin-Yi Wang, Brian Hutzen, Les Sprague, Hayley M Swain, Julia K Love, Joseph R Stanek, Louis Boon, Joe Conner, Timothy P Cripe
Oncolytic virotherapy is an effective immunotherapeutic approach for cancer treatment via a multistep process including direct tumor cell lysis, induction of cytotoxic or apoptosis-sensitizing cytokines and promotion of antitumor T cell responses. Solid tumors limit the effectiveness of immunotherapeutics in diverse ways such as secretion of immunosuppressive cytokines and expression of immune inhibitory ligands to inhibit antitumor T cell function. Blocking programmed cell death protein (PD)-1 signaling, which mediates T cell suppression via engagement of its inhibitory ligands, PD-L1 or PD-L2, is of particular interest due to recent successes in many types of cancer...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539551/suppression-of-gpi-induced-arthritis-by-oral-administration-of-transgenic-rice-seeds-expressing-altered-peptide-ligands
#15
Tomoya Hirota, Hiroto Tsuboi, Hiroyuki Takahashi, Hiromitsu Asashima, Masaru Ohta, Yuhya Wakasa, Isao Matsumoto, Fumio Takaiwa, Takayuki Sumida
OBJECTIVE: To investigate the effects and mechanisms of transgenic rice seeds expressing the altered peptide ligand (APL) of human glucose-6-phosphate-isomerase (hGPI325-339) in mice model of GPI induced arthritis (GIA). METHODS: We generated transgenic rice expressing APL12 which was analog peptide of hGPI325-339. The transgenic rice seeds were orally administered prophylactically before the induction of GIA. The severity of arthritis and titers of serum anti-GPI antibodies were evaluated...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28539427/tlr-induced-murine-dendritic-cell-dc-activation-requires-dc-intrinsic-complement
#16
Joong-Hyuk Sheen, Michael G Strainic, Jinbo Liu, Weijia Zhang, Zhengzi Yi, M Edward Medof, Peter S Heeger
Induction of proinflammatory T cell immunity is augmented by innate dendritic cell (DC) maturation commonly initiated by TLR signaling. We demonstrate that ligation of TLR3, TLR4, and TLR9 induces murine DC production of complement components and local production of the anaphylatoxin C5a. In vitro, ex vivo, and in vivo analyses show that TLR-induced DC maturation, as assessed by surface phenotype, expression profiling by gene array, and functional ability to stimulate T cell responses, requires autocrine C3a receptor and C5a receptor (C3ar1/C5ar1) signaling...
May 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28539382/il233-a-novel-il-2-and-il-33-hybrid-cytokine-ameliorates-renal-injury
#17
Marta E Stremska, Sheethal Jose, Vikram Sabapathy, Liping Huang, Amandeep Bajwa, Gilbert R Kinsey, Poonam R Sharma, Saleh Mohammad, Diane L Rosin, Mark D Okusa, Rahul Sharma
CD4(+)Foxp3(+) regulatory T cells (Tregs) protect the kidney during AKI. We previously found that IL-2, which is critical for Treg homeostasis, upregulates the IL-33 receptor (ST2) on CD4(+) T cells, thus we hypothesized that IL-2 and IL-33 cooperate to enhance Treg function. We found that a major subset of Tregs in mice express ST2, and coinjection of IL-2 and IL-33 increased the number of Tregs in lymphoid organs and protected mice from ischemia-reperfusion injury (IRI) more efficiently than either cytokine alone...
May 24, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28536578/expansion-of-cd25-negative-forkhead-box-p3-positive-t-cells-during-hiv-and-mycobacterium-tuberculosis-infection
#18
Matías T Angerami, Guadalupe V Suarez, María B Vecchione, Natalia Laufer, Diego Ameri, Graciela Ben, Hector Perez, Omar Sued, Horacio Salomón, María F Quiroga
Tuberculosis (TB) and HIV alter the immune system, and coinfected (HIV-TB) individuals usually present deregulations of T-lymphocytic immune response. We previously observed an increased frequency of "unconventional" CD4(+)CD25(-)FoxP3(+) Treg (uTreg) population during HIV-TB disease. Therefore, we aimed to explore the phenotype and function of uTreg and conventional CD4(+)CD25(+)FoxP3(+) Treg subsets (cTreg) in this context. We evaluated the expression of CD39, programmed cell death protein 1 (PD1), glucocorticoid-induced tumor necrosis factor receptor (GITR), and the effector/memory distribution by flow cytometry in cTreg and uTreg...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28536366/advances-in-the-use-of-regulatory-t-cells-for-the-prevention-and-therapy-of-graft-vs-host-disease
#19
REVIEW
Reshma Ramlal, Gerhard C Hildebrandt
Regulatory T (Tregs) cells play a crucial role in immunoregulation and promotion of immunological tolerance. Adoptive transfer of these cells has therefore been of interest in the field of bone marrow and solid organ transplantation, autoimmune diseases and allergy medicine. In bone marrow transplantation, Tregs play a pivotal role in the prevention of graft-verus-host disease (GvHD). This has generated interest in using adoptive Treg cellular therapy in the prevention and treatment of GvHD. There have been several barriers to the feasibility of Treg cellular therapy in the setting of hematopoietic stem cell transplantation (HSCT) which include low Treg concentration in peripheral blood, requiring expansion of the Treg population; instability of the expanded product with loss of FoxP3 expression; and issues related to the purity of the expanded product...
May 16, 2017: Biomedicines
https://www.readbyqxmd.com/read/28536240/reply-to-tolerogenic-insulin-peptide-therapy-precipitates-type-1-diabetes
#20
Carolin Daniel, Benno Weigmann, Harald von Boehmer
In this issue of JEM, Bergman et al. (https://doi.org/10.1084/jem.20160471) challenge the data published in our previous JEM paper on the preventive effect of tolerogenic vaccination with a strong agonist insulin mimetope in type 1 diabetes. Here, we provide a response to these data and suggest that appropriate subimmunogenic conditions are required to induce Foxp3(+) regulatory T cell conversion.
May 23, 2017: Journal of Experimental Medicine
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