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https://www.readbyqxmd.com/read/29050459/third-party-regulatory-t-cells-prevent-murine-acute-graft-versus-host-disease
#1
Jung-Yeon Lim, Keon-Il Im, Yunejin Song, Nayoun Kim, Young-Sun Nam, Young-Woo Jeon, Seok-Goo Cho
Background/Aims: Adoptive therapy with regulatory T (Treg) cells to prevent graft-versus-host disease (GVHD) would benefit from a strategy to improve homing to the sites of inflammation following hematopoietic stem cell transplantation (HSCT). Although donor-derived Treg cells have mainly been used in these models, third-party-derived Treg cells are a promising alternative for cell-based immunotherapy, as they can be screened for pathogens and cell activity, and banked for GVHD prevention...
October 19, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29048538/improvement-of-foxp3-stability-through-cns2-demethylation-by-tet-enzyme-induction-and-activation
#2
Kazue Someya, Hiroko Nakatsukasa, Minako Ito, Taisuke Kondo, Kenn-Ichi Tateda, Takashi Akanuma, Ikuko Koya, Tsukasa Sanosaka, Jun Kohyama, Yu-Ichi Tsukada, Takeji Takamura-Enya, Akihiko Yoshimura
Since induced regulatory T cells (iTregs) can be produced in a large quantity in vitro, these cells are expected to be clinically useful to induce immunological tolerance in various immunological diseases. Foxp3 (Forkhead box P3) expression in iTregs is, however, unstable due to the lack of demethylation of the CpG island in the conserved non-coding sequence 2 (CNS2) of the Foxp3 locus. To facilitate the demethylation of CNS2, we over-expressed the catalytic domain (CD) of the ten-eleven translocation (TET) protein, which catalyzes the steps of the iterative demethylation of 5-methylcytosine...
August 1, 2017: International Immunology
https://www.readbyqxmd.com/read/29035111/identification-of-atopic-dermatitis-phenotypes-with-good-responses-to-probiotics-lactobacillus-plantarum-cjlp133-in-children
#3
J Kim, B S Lee, B Kim, I Na, J Lee, J Y Lee, M R Park, H Kim, I Sohn, K Ahn
The therapeutic effect of probiotics in atopic dermatitis (AD) remains controversial and varies according to the individual patient. We aimed to identify a population of AD patients with a good clinical response to probiotic treatment. We recruited 76 children with a median age of 7.1 years who suffered from moderate to severe AD. After a 2-week washout period, all patients were given Lactobacillus plantarum CJLP133 at a dosage of 1×10(10) colony-forming units once a day for 12 weeks. We measured eosinophil counts in the peripheral blood, the proportion of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells in CD4(+) T cells, serum total immunoglobulin E (IgE) levels, and specific IgE against common allergens before the start of the treatment (T1) and at discontinuation (T2)...
October 13, 2017: Beneficial Microbes
https://www.readbyqxmd.com/read/29019858/epicutaneous-tolerance-induction-to-a-bystander-antigen-abrogates-colitis-and-ileitis-in-mice
#4
David Dunkin, M Cecilia Berin, Lucie Mondoulet, Steven Tobar, Garabet Yeretssian, Leticia Tordesillas, Alina Iuga, Thibaut Larcher, Virginia Guillespie, Pierre-Henri Benhamou, Jean-Frederic Colombel, Hugh A Sampson
BACKGROUND: Although inflammatory bowel disease (IBD) is a failure in maintaining tolerance to the intestinal microbiota, few studies have investigated the use of immunologic tolerance as a treatment approach for IBD. We hypothesized that induction of immune tolerance at a distal site could suppress intestinal inflammation through a process of bystander regulation. METHODS: Epicutaneous tolerance was induced by topical application of ovalbumin (OVA) using a Viaskin patch for 48 hours...
November 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28988508/immunological-effects-of-everolimus-in-patients-with-metastatic-renal-cell-cancer
#5
Charlotte M Huijts, Saskia J Santegoets, Tamarah D de Jong, Henk M Verheul, Tanja D de Gruijl, Hans J van der Vliet
The mammalian target of rapamycin (mTOR) is a crucial kinase present in all cells. Besides its role in the regulation of cell-growth, proliferation, angiogenesis, and survival of malignant tumors, mTOR additionally plays an important role in immune regulation by controlling the balance between effector T cells and regulatory T cells (Tregs). This critically affects the suppressive state of the immune system. Here, the systemic immunological effects of everolimus treatment were comprehensively investigated in five patients with metastatic renal cell cancer...
October 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28983404/functional-heterogeneity-of-gut-resident-regulatory-t-cells
#6
REVIEW
Maik Luu, Ulrich Steinhoff, Alexander Visekruna
Regulatory T cells (Treg cells) have a central role in the maintenance of intestinal homeostasis by restraining inappropriate immune responses in the healthy gut. Although distinct intestinal immune cell populations have been described to exhibit regulatory activity, several genetic and functional studies provided a strong evidence for a pivotal role of forkhead box P3 (Foxp3)(+)CD4(+) Treg cells in prevention of dysregulated mucosal immune reactions and development of chronic immunological disorders such as celiac disease, food allergies and inflammatory bowel disease...
September 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28983403/autoimmunity-inflammation-in-a-monogenic-primary-immunodeficiency-cohort
#7
William Rae, Daniel Ward, Christopher J Mattocks, Yifang Gao, Reuben J Pengelly, Sanjay V Patel, Sarah Ennis, Saul N Faust, Anthony P Williams
Primary immunodeficiencies (PIDs) are rare inborn errors of immunity that have a heterogeneous phenotype that can include severe susceptibility to life-threatening infections from multiple pathogens, unique sensitivity to a single pathogen, autoimmune/inflammatory (AI/I) disease, allergies and/or malignancy. We present a diverse cohort of monogenic PID patients with and without AI/I diseases who underwent clinical, genetic and immunological phenotyping. Novel pathogenic variants were identified in IKBKG, CTLA4, NFKB1, GATA2, CD40LG and TAZ as well as previously reported pathogenic variants in STAT3, PIK3CD, STAT1, NFKB2 and STXBP2...
September 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28983301/immunological-changes-in-blood-of-newborns-exposed-to-anti-tnf-%C3%AE-during-pregnancy
#8
Ana Esteve-Solé, Àngela Deyà-Martínez, Irene Teixidó, Elena Ricart, Macarena Gompertz, Maria Torradeflot, Noemí de Moner, Europa Azucena Gonzalez, Ana Maria Plaza-Martin, Jordi Yagüe, Manel Juan, Laia Alsina
BACKGROUND: Although anti-TNF-α monoclonal antibodies are considered safe during pregnancy, there are no studies on the development of the exposed-infant immune system. The objective was to study for the first time the impact of throughout pregnancy exposure to anti-TNF-α has an impact in the development of the infant's immune system, especially B cells and the IL-12/IFN-γ pathway. METHODS: Prospective study of infants born to mothers with inflammatory bowel disease treated throughout pregnancy with anti-TNF-α (adalimumab/infliximab)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28982868/peripheral-tr1-and-foxp3-treg-as-markers-of-recurrent-malignancies-in-patients-with-hepato-biliary-pancreatic-cancers
#9
Tetsuya Ikemoto, Mitsuo Shimada, Daichi Ishikawa, Yoichiro Kawashita, Hiroki Teraoku, Masato Yoshikawa, Shinichiro Yamada, Y U Saito, Yuji Morine, Satoru Imura
BACKGROUND/AIM: Recently CD4(+)CD49b(+) LAG3(+)regulatory T (Tr1) cells are reported to be IL-10 driven, have strong regulatory activities. Thus, this study aimed to investigate whether Treg and Tr1 cells participate in immunological status against cancer. PATIENTS AND METHODS: Peripheral blood was withdrawn from patients (n=78), and healthy volunteers as controls (n=23). The peripheral blood mononuclear cells were subjected to FACScan analysis after labeling with anti-CD4, -CD25, - Foxp3, -CD49b and -LAG3 antibodies...
October 2017: Anticancer Research
https://www.readbyqxmd.com/read/28978806/dock8-enforces-immunological-tolerance-by-promoting-il-2-signaling-and-immune-synapse-formation-in-tregs
#10
Erin Janssen, Sudha Kumari, Mira Tohme, Sumana Ullas, Victor Barrera, Jeroen Mj Tas, Marcela Castillo-Rama, Roderick T Bronson, Shariq M Usmani, Darrell J Irvine, Thorsten R Mempel, Raif S Geha
Patients deficient in the guanine nucleotide exchange factor DOCK8 have decreased numbers and impaired in vitro function of Tregs and make autoantibodies, but they seldom develop autoimmunity. We show that, similarly, Dock8-/- mice have decreased numbers and impaired in vitro function of Tregs but do not develop autoimmunity. In contrast, mice with selective DOCK8 deficiency in Tregs develop lymphoproliferation, autoantibodies, and gastrointestinal inflammation, despite a normal percentage and in vitro function of Tregs, suggesting that deficient T effector cell function might protect DOCK8-deficient patients from autoimmunity...
October 5, 2017: JCI Insight
https://www.readbyqxmd.com/read/28967957/colon-immune-related-adverse-events-anti-ctla-4-and-anti-pd-1-blockade-induce-distinct-immunopathological-entities
#11
Clélia Coutzac, Julien Adam, Emilie Soularue, Michael Collins, Antoine Racine, Charlotte Mussini, Lisa Boselli, Nyam Kamsukom, Christine Mateus, Mélinda Charrier, Lydie Cassard, David Planchard, Vincent Ribrag, Karim Fizazi, Yohann Loriot, Patricia Lepage, Jean-Yves Scoazec, Caroline Robert, Franck Carbonnel, Nathalie Chaput
Background and Aim: Immune checkpoint inhibitors targeting CTLA-4 and PD-1 improve survival in cancer patients but may induce immune-related adverse events, including colitis. The immunological characteristics of anti-CTLA-4 [αCTLA-4]- and anti-PD-1 [αPD-1]-related colitis have been poorly described. The aim of the present study was to compare the immunological and histological characteristics of αCTLA-4-induced colitis and αPD-1-induced colitis. Methods: Colonic biopsies from patients with αCTLA-4-induced colitis, αPD-1-induced colitis, and inflammatory bowel disease [IBD] were analysed by immunohistochemistry and flow cytometry...
October 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28958903/th17-cells-mediate-inflammation-in-a-novel-model-of-spontaneous-experimental-autoimmune-lacrimal-keratoconjunctivitis-with-neural-damage
#12
Kyoung Yul Seo, Kazuya Kitamura, Soo Jung Han, Brian Kelsall
BACKGROUND: Dry eye disease (DED) affects one third of population worldwide. In prior studies, experimental autoimmune lacrimal keratoconjunctivitis (EALK) induced by desiccating stress in mice has been used as a model of DED. This model is complicated by a requirement for exogenous epithelial cell injury and the administration of anticholinergic agents that have broad immunological effects. OBJECTIVE: We sought to develop a novel mouse model of EALK, and to demonstrate the responsible immunological pathogenic mechanisms...
September 25, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28951518/immune-activation-in-early-stage-non-small-cell-lung-cancer-patients-receiving-neoadjuvant-chemotherapy-plus-ipilimumab
#13
John S Yi, Neal Ready, Patrick Healy, Chelsae Dumbauld, Robyn Osborne, Mark Berry, Debra Shoemaker, Jeffrey Clarke, Jeffrey Crawford, Betty C Tong, David Harpole, Thomas A D'Amico, Frances McSherry, Frank Dunphy, Shannon J McCall, Jared D Christensen, Xiaofei Wang, Kent J Weinhold
PURPOSE: To determine the immunologic effects of neoadjuvant chemotherapy plus ipilimumab in early stage non-small cell lung cancer (NSCLC) patients. EXPERIMENTAL DESIGN: This is a single-arm chemotherapy plus phased ipilimumab Phase II study of 24 treatment-naïve patients with Stage IB-IIIA NSCLC. Patients received neoadjuvant therapy consisting of 3 cycles of paclitaxel with either cisplatin or carboplatin and ipilimumab included in the last 2 cycles. RESULTS: Chemotherapy alone had little effect on immune parameters in PBMCs...
September 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28931653/combined-ox40l-and-mtor-blockade-controls-effector-t-cell-activation-while-preserving-treg-reconstitution-after-transplant
#14
Victor Tkachev, Scott N Furlan, Benjamin Watkins, Daniel J Hunt, Hengqi Betty Zheng, Angela Panoskaltsis-Mortari, Kayla Betz, Melanie Brown, John B Schell, Katie Zeleski, Alison Yu, Ian Kirby, Sarah Cooley, Jeffrey S Miller, Bruce R Blazar, Duncan Casson, Phil Bland-Ward, Leslie S Kean
A critical question facing the field of transplantation is how to control effector T cell (Teff) activation while preserving regulatory T cell (Treg) function. Standard calcineurin inhibitor-based strategies can partially control Teffs, but breakthrough activation still occurs, and these agents are antagonistic to Treg function. Conversely, mechanistic target of rapamycin (mTOR) inhibition with sirolimus is more Treg-compatible but is inadequate to fully control Teff activation. In contrast, blockade of OX40L signaling has the capacity to partially control Teff activation despite maintaining Treg function...
September 20, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28930796/navigating-t-cell-immunometabolism-in-transplantation
#15
Naoki Tanimine, Laurence A Turka, Bhavana Priyadharshini
Recently, a new discipline termed "immunometabolism" has transformed the field of immunology. It encompasses the study of the intrinsic metabolic pathways of different immune subsets and their impact on cellular fate and function. For instance, broadly speaking, pro-inflammatory cells depend upon glycolysis and glutamine oxidation while cells involved in anti-inflammatory response such as Foxp3+ regulatory T cells (Tregs) utilize predominantly fatty acid oxidation. However, while a useful paradigm, this actually is a reductionist view and the engagement of these metabolic pathways is not mutually exclusive between these subsets...
September 19, 2017: Transplantation
https://www.readbyqxmd.com/read/28930556/osteoimmunology-the-nexus-between-bone-and-immune-system
#16
Hamid Y Dar, Zaffar Azam, Rajaneesh Anupam, Rajesh K Mondal, Rupesh K Srivastava
Osteoimmunology is an interdisciplinary research field which combines the existing fields of osteology (bone biology) and immunology under one umbrella. The observation that contributed enormously to the emergence of osteoimmunology as an independent field of investigation was the enhanced bone loss in various inflammatory bone diseases such as rheumatoid arthritis, osteoporosis and periodontitis. T helper cells (Th1, Th2, Treg and Th17) along with various other immune cells (B cells, DC, macrophages etc.) are actively involved in bone homeostasis...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28898532/immunological-efficacy-of-herbal-medicines-in-prostate-cancer-patients-treated-by-personalized-peptide-vaccine
#17
Noriko Koga, Fukuko Moriya, Kayoko Waki, Akira Yamada, Kyogo Itoh, Masanori Noguchi
This randomized phase II study investigated the immunological efficacy of herbal medicines (HM) using Hochu-ekki-to and Keishi-bukuryo-gan in combination with personalized peptide vaccination (PPV) for castration-resistant prostate cancer (CRPC). Seventy patients with CRPC were assigned to two arms; PPV plus HM or PPV alone. Two to four peptides were chosen from 31 peptides derived from cancer antigens for a s.c. injection of PPV given eight times according to the patient's human leukocyte antigen type and levels of antigen-specific IgG titer before PPV treatment...
September 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28894447/the-microbial-metabolite-butyrate-induces-expression-of-th1-associated-factors-in-cd4-t-cells
#18
Meike Kespohl, Niyati Vachharajani, Maik Luu, Hani Harb, Sabine Pautz, Svenja Wolff, Nina Sillner, Alesia Walker, Philippe Schmitt-Kopplin, Thomas Boettger, Harald Renz, Stefan Offermanns, Ulrich Steinhoff, Alexander Visekruna
Short-chain fatty acids (SCFAs), which are generated by the bacterial fermentation of dietary fibers, promote expansion of regulatory T cells (Tregs). Potential therapeutic value of SCFAs has been recently highlighted in the experimental models of T cell-mediated autoimmunity and allergic inflammation. These studies suggest that physiological intestinal concentrations of SCFAs within the millimolar range are crucial for dampening inflammation-mediated processes. Here, we describe opposing effects of SCFAs on T cell-mediated immune responses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28890543/the-altered-pd-1-pd-l1-pathway-delivers-the-one-two-punch-effects-to-promote-the-treg-th17-imbalance-in-pre-eclampsia
#19
Yonghong Zhang, Zhaozhao Liu, Mei Tian, Xiaohui Hu, Liling Wang, Jinlu Ji, Aihua Liao
The programmed cell death-1 (PD-1)/PD-ligand 1 (PD-L1) pathway is critical for normal pregnancy by promoting regulatory T (Treg) cell development and inhibiting the Th17 response. However, the relationship between the PD-1/PD-L1 pathway and the Treg/Th17 imbalance in pre-eclampsia (PE) is an enigma. In this study, decreased PD-1 and PD-L1 expression and a Treg/Th17 imbalance were observed at the maternal-fetal interface in PE. The regulatory effects of the PD-1/PD-L1 pathway on the Treg and Th17 cell quantities were determined in vitro by targeting T-cell proliferation, differentiation and transdifferentiation...
September 11, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28877578/syphacia-obvelata-a-new-hope-to-induction-of-intestinal-immunological-tolerance-in-c57bl-6-mice
#20
Niloofar Taghipour, Nariman Mosaffa, Mohammad Rostami-Nejad, Mohamad Mohsen Homayoni, Esmaeil Mortaz, Hamid Asadzadeh Aghdaei, Mohammad Reza Zali
The ability of nematodes to manipulate the immune system of their host towards a Th2 and T regulatory responses has been proposed to suppress the inflammatory response. Clinical trials have proposed a useful effect of helminth infections on improvement of inflammatory disorders. In this study, we investigated the immunomodulatory effect of Syphacia obvelata infection to induce intestinal tolerance in C57BL/6 mice. Mice were infected through the cagemates with self-infected BALB/c mice. Four weeks post-infection, expression levels of IFN-γ, TNF-α, IL-17, and IL-10 were assessed in the supernatant of mesenteric lymph node (MLN) culture...
August 2017: Korean Journal of Parasitology
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