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https://www.readbyqxmd.com/read/29141242/chloroquine-autophagic-inhibition-rebalances-th17-treg-mediated-immunity-and-ameliorates-systemic-lupus-erythematosus
#1
Ning An, Yanwen Chen, Chao Wang, Chen Yang, Zhi-Hong Wu, Jing Xue, Lin Ye, Shujun Wang, Hua-Feng Liu, Qingjun Pan
BACKGROUND: Imbalanced cellular immunity is critical to the pathogenesis of systemic lupus erythematosus (SLE). Recently, autophagy has emerged as a key homeostatic mechanism in T lymphocytes. This study was conducted to explore the impact of autophagy on the Th17/ regulatory T (Treg) immune imbalance in SLE. METHODS: Peripheral Th17 and Treg cells from newly diagnosed patients with SLE and healthy controls were detected by flow cytometry. Additionally, the effects of chloroquine (CQ) autophagic inhibition on the Th17/Treg immune response were investigated in vitro...
November 14, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29141218/reciprocal-expression-of-il-35-and-il-10-defines-two-distinct-effector-treg-subsets-that-are-required-for-maintenance-of-immune-tolerance
#2
Xundong Wei, Jianhua Zhang, Qianchong Gu, Man Huang, Wei Zhang, Jie Guo, Xuyu Zhou
Regulatory T cells (Tregs) can exert their functions through multiple suppressive mechanisms; however, it is unclear how Tregs exactly employ these mechanisms. In this study, we found that interleukin-35 (IL-35)-producing Tregs were a distinct effector population from the IL-10-producing subset. We also revealed that these two subsets of effector Tregs have different transcription factor dependency. Terminal differentiation regulator Blimp1 was only critical for IL-10 production, but not for IL-35; Foxp3 was essential for IL-35 but dispensable for IL-10 production...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29141216/slc3a2-mediates-branched-chain-amino-acid-dependent-maintenance-of-regulatory-t-cells
#3
Kayo Ikeda, Makoto Kinoshita, Hisako Kayama, Shushi Nagamori, Pornparn Kongpracha, Eiji Umemoto, Ryu Okumura, Takashi Kurakawa, Mari Murakami, Norihisa Mikami, Yasunori Shintani, Satoko Ueno, Ayatoshi Andou, Morihiro Ito, Hideki Tsumura, Koji Yasutomo, Keiichi Ozono, Seiji Takashima, Shimon Sakaguchi, Yoshikatsu Kanai, Kiyoshi Takeda
Foxp3(+) regulatory T (Treg) cells, which suppress immune responses, are highly proliferative in vivo. However, it remains unclear how the active replication of Treg cells is maintained in vivo. Here, we show that branched-chain amino acids (BCAAs), including isoleucine, are required for maintenance of the proliferative state of Treg cells via the amino acid transporter Slc3a2-dependent metabolic reprogramming. Mice fed BCAA-reduced diets showed decreased numbers of Foxp3(+) Treg cells with defective in vivo proliferative capacity...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29140829/guiding-regulatory-t-cells-to-the-allograft
#4
Caroline Lamarche, Megan K Levings
PURPOSE OF REVIEW: The application of regulatory T cell (Treg) therapy in organ transplantation is actively being pursued using unmodified, typically polyclonal cells. As the results of these ongoing clinical trials emerge, it is time to plan the next wave of clinical trials of Tregs. Here we will review a key strategy to improve Treg effectiveness and reduce side effects, namely increasing Treg specificity - both in terms of antigen recognition and localization to the allograft. RECENT FINDINGS: Study of chemokine signatures accompanying acute rejection has revealed several chemokines that could be targeted to increase Treg homing...
November 14, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/29140541/regulatory-t-cells-in-acute-dengue-viral-infection
#5
Eresha Jayaratne, Dulharie Wijeratne, Samitha Fernando, Achala Kamaladasa, Laksiri Gomes, Ananda Wijewickrama, Graham Stuart Ogg, Gathsaurie Neelika Malavige
Although regulatory T cells (Tregs) have been shown to be expanded in acute dengue, their role in pathogenesis and their relationship to clinical disease severity, and extent of viraemia have not been fully evaluated. The frequency of Tregs was assessed in 56 adult patients with acute dengue, by determining the proportion of FOXP3 expressing CD4(+) CD25(+) T cells (FOXP3+ cells). DENV viral loads were measured by quantitative real time PCR and DENV specific T cell responses were measured by ex vivo IFNγ ELISpot assays to overlapping peptide pools of DENV-NS3, NS1 and NS5...
November 15, 2017: Immunology
https://www.readbyqxmd.com/read/29138503/dihydrotestosterone-levels-at-birth-associate-positively-with-higher-proportions-of-circulating-immature-na%C3%A3-ve-cd5-b-cells-in-boys
#6
Anna-Carin Lundell, Inger Nordström, Kerstin Andersson, Anna Strömbeck, Claes Ohlsson, Åsa Tivesten, Anna Rudin
Boys present with higher proportions of immature/naïve CD5(+) B cells than girls up to 3 years of age. Boys also have higher fractions of regulatory T cells (Tregs) in early infancy, but the mechanisms for these sex-related differences are unknown. In the prospective FARMFLORA follow-up study of 23 boys and 25 girls, we investigated if these immunological differences remained at 8 years of age. We also examined if testosterone or dihydrotestosterone (DHT) levels at birth and at 8 years of age were associated with immune maturation...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29137411/a-novel-polyamine-blockade-therapy-activates-an-anti-tumor-immune-response
#7
Eric T Alexander, Allyson Minton, Molly C Peters, Otto Phanstiel, Susan K Gilmour
Most tumors maintain elevated levels of polyamines to support their growth and survival. This study explores the anti-tumor effect of polyamine starvation via both inhibiting polyamine biosynthesis and blocking the upregulated import of polyamines into the tumor. We demonstrate that polyamine blockade therapy (PBT) co-treatment with both DFMO and a novel polyamine transport inhibitor, Trimer PTI, significantly inhibits tumor growth more than treatment with DFMO or the Trimer PTI alone. The anti-tumor effect of PBT was lost in mice where CD4(+) and CD8(+) T cells were antibody depleted, implying that PBT stimulates an anti-tumor immune effect that is T-cell dependent...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136784/the-alternation-of-autophagy-apoptosis-in-cd4-cd25-foxp3-tregs-on-the-developmental-stages-of-atherosclerosis
#8
Yuling Tian, Xiao Liang, Yue Wu
Naturally regulatory T cells (Tregs) play a critical role in the regulation of T cell-mediated immune responses in atherosclerosis. However, the regulatory mechanism underlying Tregs upon long-term development of atherosclerosis remains unknown. Therefore, in this study, atherosclerotic model was induced in ApoE-/- mice by feeding fat-diet for 10 weeks. Quantification of atherosclerotic lesions was done by calculating the lesion size in the aortic sinus every 2 weeks. The lipid levels and inflammatory mediators were detected in serum sample...
November 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29136677/thymus-growth-and-fetal-immune-responses-in-diabetic-pregnancies
#9
Katharina Warncke, Ramona Lickert, Stephanie Eitel, Karl-Philipp Gloning, Ezio Bonifacio, Eva-Maria Sedlmeier, Petra Becker, Jan Knoop, Andreas Beyerlein, Anette-Gabriele Ziegler
Type 1 diabetes (T1D) during pregnancy possibly affects the development of the thymus and the maturation of the immune system in the offspring. The aim of the ImmunDiabRisk study was to investigate thymus growth and maternal and fetal immune responses in pregnancies with and without T1D. The thymus circumferences of the fetuses of pregnant women with T1D (n=49) and without diabetes (n=59) were measured using ultrasound around the 29th gestational week and standardized for gestational age. Simultaneously, the frequencies and total numbers of cell markers were analyzed by flow cytometry in maternal peripheral blood, and at birth in umbilical cord blood...
November 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29136611/gut-microbiota-in-health-and-disease
#10
Yuichiro Yamashiro
Intestinal regulatory T (Treg) cells are critical to maintaining immune tolerance to dietary antigens and gut microbiota. This paper reviews several papers on this topic that were recently published by Japanese researchers. Specifically, Prof. K. Honda and his group have found that commensal microbiota capable of metabolizing butyrate induces the differentiation of colonic Treg cells. In a separate work, Prof. Y. Yokoyama and his group used a novel, culture-independent analytical method (the Yakult Intestinal Flora-Scan) for detection of bacteria in the bloodstream...
November 14, 2017: Annals of Nutrition & Metabolism
https://www.readbyqxmd.com/read/29135830/tissue-resident-lymphocytes-in-solid-organ-transplantation-innocent-passengers-or-the-key-to-organ-transplant-survival
#11
Amy C Prosser, Axel Kallies, Michaela Lucas
Short-term outcomes of solid organ transplantation have improved dramatically over the past several decades; however, long-term survival has remained static over the same time period, and chronic rejection remains a major cause of graft failure. The importance of donor, or 'passenger', lymphocytes to the induction of tolerance to allografts was recognized in the 1990s; however, their precise contribution to graft acceptance or rejection has not been elucidated. Recently, specialized populations of tissue-resident lymphocytes in nonlymphoid organs have been described...
November 14, 2017: Transplantation
https://www.readbyqxmd.com/read/29133367/regulatory-t-cell-genes-drive-altered-immune-microenvironment-in-adult-solid-cancers-and-allow-for-immune-contextual-patient-subtyping
#12
Jurriaan Brouwer-Visser, Wei-Yi Cheng, Anna Bauer-Mehren, Daniela Maisel, Katharina Lechner, Emilia Andersson, Joel T Dudley, Francesca Milletti
BACKGROUND: The tumor microenvironment is an important factor in cancer immunotherapy response. To further understand how a tumor affects the local immune system, we analyzed immune gene expression differences between matching normal and tumor tissue. METHODS: We analyzed public and new gene expression data from solid cancers and isolated immune cell populations. We also determined the correlation between CD8, FoxP3 immunohistochemistry (IHC) and our gene signatures...
November 13, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/29132961/title-experimental-asthma-persists-in-il33-receptor-knockout-mice-due-to-the-emergence-of-a-tslp-driven-il9-and-il13-ilc2-subpopulations
#13
Mukesh Verma, Sucai Liu, Lidia Michalec, Anand Sripada, Magdalena M Gorska, Rafeul Alam
BACKGROUND: IL33 plays an important role in development of experimental asthma. OBJECTIVE: To study the role of the IL33 receptor (ST2) in persistence of asthma in a mouse model. METHODS: We studied allergen-induced experimental asthma in ST2 knockout (KO) and wild-type control mice. We measured airway hyperresponsiveness (AHR) by flexivent, inflammatory indices by ELISA, histology and real-time PCR, and ILC2s in lung single cell preparations by flow cytometry...
November 10, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29132705/il-17a-improves-the-efficacy-of-mesenchymal-stem%C3%A2-cells-in-ischemic-reperfusion-renal-injury%C3%A2-by%C3%A2-increasing-treg-percentages-by-the%C3%A2-cox-2-pge2%C3%A2-pathway
#14
Ming Bai, Li Zhang, Bo Fu, Jiuxu Bai, Yingjie Zhang, Guangyan Cai, Xueyuan Bai, Zhe Feng, Shiren Sun, Xiangmei Chen
Mesenchymal stem cells (MSCs) are effective for the management of experimental ischemia-reperfusion acute kidney injury (IRI-AKI). Immune modulation is one of the important mechanisms of MSCs treatment. Interleukin-17A (IL-17A) pretreated MSCs are more immunosuppressive with minimal changes in immunogenicity in vitro. Here, we demonstrated that administration of IL-17A-pretreated MSCs resulted in significantly lower acute tubular necrosis scores, serum creatinine, and BUN of mice with IRI-AKI, compared with the administration of MSCs...
November 11, 2017: Kidney International
https://www.readbyqxmd.com/read/29130799/allergen-immunotherapy-modulates-sensitivity-of-treg-cells-to-apoptosis-in-a-rat-model-of-allergic-asthma
#15
Ankur Datta, Saibal Moitra, Prasanta K Das, Somnath Mondal, Sk Md Omar Faruk, Iman Hazra, Santanu K Tripathi, Swapna Chaudhuri
AIM: To study the apoptosis of Foxp3(+) Treg cells following Alstonia scholaris pollen sensitization-challenge and following allergen immunotherapy. MATERIALS & METHODS: Wistar rats were sensitized-challenged with Alstonia scholaris pollen and were further given intranasal immunotherapy. For the analysis of the apoptotic proteins on Treg cells by flow cytometry, multiple gating procedures were followed. RESULTS: Allergen sensitization-challenge increases Annexin-V, Fas, FasL, caspases-8, 9, 3 cytochrome-C, APAF-1, Bax, perforin-1 and granzyme-B on Treg cells which is decreased following intranasal immunotherapy...
November 2017: Immunotherapy
https://www.readbyqxmd.com/read/29130617/dendritic-cell-phenotype-in-severe-asthma-reflects-clinical-responsiveness-to-glucocorticoids
#16
Emma S Chambers, Alexandra M Nanzer, Paul E Pfeffer, David F Richards, Adrian R Martineau, Christopher J Griffiths, Christopher J Corrigan, Catherine M Hawrylowicz
BACKGROUND: Subsets of patients with severe asthma remain symptomatic despite prolonged, high dosage glucocorticoid therapy. We hypothesised that the clinical glucocorticoid sensitivity of these asthmatics is reflected in differences in peripheral blood dendritic cell subsets. OBJECTIVE: To compare peripheral blood leukocyte populations using flow cytometry at baseline and after 2 weeks of systemic glucocorticoid (steroid) treatment to identify immunological differences between steroid sensitive (SS) and steroid resistant (SR) asthmatics...
November 11, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29129918/intratumoral-cd40-activation-and-checkpoint-blockade-induces-t-cell-mediated-eradication-of-melanoma-in-the-brain
#17
Manisha Singh, Christina Vianden, Mark J Cantwell, Zhimin Dai, Zhilan Xiao, Meenu Sharma, Hiep Khong, Ashvin R Jaiswal, Faisal Faak, Yared Hailemichael, L M E Janssen, Uddalak Bharadwaj, Michael A Curran, Adi Diab, Roland L Bassett, David J Tweardy, Patrick Hwu, Willem W Overwijk
CD40 agonists bind the CD40 molecule on antigen-presenting cells and activate them to prime tumor-specific CD8(+) T cell responses. Here, we study the antitumor activity and mechanism of action of a nonreplicating adenovirus encoding a chimeric, membrane-bound CD40 ligand (ISF35). Intratumoral administration of ISF35 in subcutaneous B16 melanomas generates tumor-specific, CD8(+) T cells that express PD-1 and suppress tumor growth. Combination therapy of ISF35 with systemic anti-PD-1 generates greater antitumor activity than each respective monotherapy...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29129697/dual-mechanisms-for-balancing-th17-and-treg-cell-fate-by-creb
#18
Antony Symons, Wenjun Ouyang
Th17 cells, which express the cytokine IL-17A, and master regulator RORγt, are important in the inflammatory response to fungal and bacterial pathogens, but also have a pathogenic role in many inflammatory disorders. In contrast, regulatory T cells (Treg), expressing the Foxp3 transcription factor, have a suppressive function and can dampen an immune response. The appropriate balance of these distinct effector functions is critical for an effective immune response and autoimmunity can arise if this process goes awry...
November 9, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29129023/pathomechanisms-of-contact-sensitization
#19
REVIEW
Philipp R Esser, Stefan F Martin
Contact sensitization is the initial process involved in the development of an allergic reaction to xenobiotic environmental substances. Here, we briefly describe the differences between irritant and allergic contact dermatitis. Then, we highlight the essential steps involved in the development of an ACD reaction, i.e., the protein binding of haptens, genetic factors influencing the penetration of sensitizers into the skin, the different mechanisms driving the initial development of an inflammatory cytokine micromilieu enabling the full maturation of dendritic cells, the role of pre- and pro-haptens, antigen presentation and T cell activation via MHC and CD1 molecules, dendritic cell (DC) migration, and potential LC contribution as well as the different T cell subsets involved in ACD...
November 11, 2017: Current Allergy and Asthma Reports
https://www.readbyqxmd.com/read/29127350/memory-regulatory-t-cells-increase-only-in-inflammatory-phase-of-chronic-hepatitis-b-infection-and-related-to-galectin-9-tim-3-interaction
#20
Ching-Chih Hu, Wen-Juei Jeng, Yi-Cheng Chen, Jian-He Fang, Chien-Hao Huang, Wei Teng, Yi-Chung Hsieh, Yung-Chang Lin, Rong-Nan Chien, I-Shyan Sheen, Chun-Yen Lin
CD4(+)Foxp3(+) regulatory T cells (Tregs) are the main immune suppressors with subpopulation of inflamed-tissue related memory Tregs (mTregs) and non-related resting Treg (rTregs). Previously, Treg was proposed to be the cause of chronicity of hepatitis B virus (HBV) infection but with controversies. We then investigated the role of mTregs in distinct immune phases of chronic HBV infection, especially the non-inflammatory versus inflammatory phases. It was found mTregs but not rTregs increased only in the inflammatory phase and correlated with serum alanine aminotransferase (ALT) level...
November 10, 2017: Scientific Reports
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