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https://www.readbyqxmd.com/read/29225189/luteolin-attenuates-airway-inflammation-by-inducing-the-transition-of-cd4-cd25-to-cd4-cd25-regulatory-t-cells
#1
Seung-Hyung Kim, Evelyn Saba, Bok-Kyu Kim, Won-Kyung Yang, Yang-Chun Park, Han Jae Shin, Chang Kyun Han, Young Cheol Lee, Man Hee Rhee
Regulatory T cells (Th2) play an important role in autoimmunity and have been shown to exert anti-inflammatory effects in allergic asthma. Mouse model of airway inflammation was used to examine the suppressive activity of luteolin-induced CD4+CD25+ regulatory T cells (Tregs) in vivo. In this study, BALB/c mice were sensitized with ovalbumin antigen (OVA) by aerosol challenge. Then, various biological processes were examined, including airway eosinophilia; mucus hypersecretion; elevation of OVA-specific IgE, expression of Th2 cytokines and chemokine levels; expression of eotaxin 2 and CCR3; and airway hyper responsiveness (AHR)...
December 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29208963/enhanced-cd25-foxp3-regulatory-t-cell-development-by-amodiaquine-through-activation-of-nuclear-receptor-4a
#2
Hee Yeon Won, Ji Hyun Shin, Sera Oh, Hana Jeong, Eun Sook Hwang
CD4+ T cells play key roles in the regulation of immune responses against pathogenic infectious antigens via development into effector T helper and induced regulatory T (iTreg) cells. Particularly, CD4+CD25+Foxp3+ iTreg cells are crucial for maintaining immune homeostasis and controlling inflammatory diseases. Anti-inflammatory drugs that enhance iTreg cell generation would be effective at preventing and treating inflammatory and autoimmune diseases. In this study, we examined whether anti-malarial and anti-arthritic amodiaquine (AQ) could affect iTreg cell development...
December 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29180394/redirecting-tgf-%C3%AE-signaling-through-the-%C3%AE-catenin-foxo-complex-prevents-kidney-fibrosis
#3
Xi Qiao, Padmashree Rao, Yun Zhang, Lixin Liu, Min Pang, Hailong Wang, Min Hu, Xinrui Tian, Jianlin Zhang, Ye Zhao, Xin Maggie Wang, Chengshi Wang, Hong Yu, Fei Guo, Qi Cao, Yiping Wang, Yuan Min Wang, Geoff Yu Zhang, Vincent W Lee, Stephen I Alexander, Guoping Zheng, David C H Harris
TGF-β is a key profibrotic factor, but targeting TGF-β to prevent fibrosis also abolishes its protective anti-inflammatory effects. Here, we investigated the hypothesis that we can redirect TGF-β signaling by preventing downstream profibrotic interaction of β-catenin with T cell factor (TCF), thereby enhancing the interaction of β-catenin with Foxo, a transcription factor that controls differentiation of TGF-β induced regulatory T cells (iTregs), and thus, enhance anti-inflammatory effects of TGF-β In iTregs derived from EL4 T cells treated with recombinant human TGF-β1 (rhTGF-β1) in vitro, inhibition of β-catenin/TCF transcription with ICG-001 increased Foxp3 expression, interaction of β-catenin and Foxo1, binding of Foxo1 to the Foxp3 promoter, and Foxo transcriptional activity...
November 27, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29143918/induction-of-cd4-cd25-foxp3-regulatory-t-cells-by-mesenchymal-stem-cells-is-associated-with-runx-complex-factors
#4
Maryam Khosravi, Ali Bidmeshkipour, Ali Moravej, Suzzan Hojjat-Assari, Sina Naserian, Mohammad Hossein Karimi
Among the particular immunomodulation properties of mesenchymal stem cells (MSCs), one relies on their capacity to regulatory T cell (Treg) induction from effector T cells. Stable expression of Foxp3 has a dominant role in suppressive phenotype and stability of induced regulatory T cells (iTregs). How MSCs induce stable Foxp3 expression in iTregs remains unknown. We previously showed MSCs could enhance demethylation of Treg-specific demethylated region (TSDR) in iTregs in cell-cell contact manner (unpublished data)...
November 16, 2017: Immunologic Research
https://www.readbyqxmd.com/read/29126851/ccr6-signaling-inhibits-suppressor-function-of-induced-treg-during-gut-inflammation
#5
Neeraja Kulkarni, Heikrujam Thoihen Meitei, Sandip Ashok Sonar, Praveen Kumar Sharma, Vikkarasan Rehman Mujeeb, Sharad Srivastava, Ramanamurthy Boppana, Girdhari Lal
CCR6 is a G protein-coupled receptor (GPCR) that binds to a specific chemokine, CCL20. The role of CCR6-CCL20 is very well studied in the migration of immune cells, but the non-chemotaxis functions of CCR6 signaling were not known. Here, we show that during gut inflammation, the frequency of Foxp3(+)CD4(+) T cells (Tregs) reduced in the secondary lymphoid tissues and CCR6(+) Tregs enhanced the expression of RORγt. The peripheral blood mononuclear cells (PBMCs) of ulcerative colitis (UC) patients showed lower percentages of Foxp3(+)CD4(+) T cells, as compared to healthy individuals, with CCR6(+) Tregs showing higher RORγt expression as compared to CCR6(-)Tregs...
November 7, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29126272/generation-of-alloantigen-specific-induced-treg-stabilized-by-vitamin-c-treatment-and-its-application-for-prevention-of-acute-graft-versus-host-disease-model
#6
Hidenori Kasahara, Taisuke Kondo, Hiroko Nakatsukasa, Shunsuke Chikuma, Minako Ito, Makoto Ando, Yutaka Kurebayashi, Takashi Sekiya, Taketo Yamada, Shinichiro Okamoto, Akihiko Yoshimura
Antigen-specific regulatory T cells (Tregs) possess the potential to reduce excess immune responses in autoimmune diseases, allergy, rejection after organ transplantation, and graft-versus-host disease (GVHD) in hematopoietic stem-cell transplantation. Although in vitro-expanded antigen-specific induced Tregs (iTregs) have been considered to be a promising therapeutic agent against such excessive immune reactions, the instability of iTregs after transfer is a fundamental problem in their clinical application...
November 4, 2017: International Immunology
https://www.readbyqxmd.com/read/29066254/ci8-short-a-novel-lps-induced-peptide-from-the-ascidian-ciona-intestinalis-modulates-responses-of-the-human-immune-system
#7
Angela Bonura, Aiti Vizzini, Sara Vlah, Francesco Gervasi, Alessandra Longo, Mario R Melis, Frank A Schildberg, Paolo Colombo
The selective modulation of immunity is an emerging concept driven by the vast advances in our understanding of this crucial host defense system. Invertebrates have raised researchers' interest as potential sources of new bioactive molecules owing to their antibacterial, anticancer and immunomodulatory activities. A LipoPolySaccharide (LPS) challenge in the ascidian Ciona intestinalis generates the transcript, Ci8 short, with cis-regulatory elements in the 3' UTR region that are essential for shaping innate immune responses...
October 16, 2017: Immunobiology
https://www.readbyqxmd.com/read/29066174/attenuation-of-cd4-cd25-regulatory-t-cells-in-the-tumor-microenvironment-by-metformin-a-type-2-diabetes-drug
#8
Yuki Kunisada, Shingo Eikawa, Nahoko Tomonobu, Shohei Domae, Takenori Uehara, Shohei Hori, Yukihiro Furusawa, Koji Hase, Akira Sasaki, Heiichiro Udono
CD4+CD25+ regulatory T cells (Treg), an essential subset for preventing autoimmune diseases, is implicated as a negative regulator in anti-tumor immunity. We found that metformin (Met) reduced tumor-infiltrating Treg (Ti-Treg), particularly the terminally-differentiated CD103+KLRG1+ population, and also decreased effector molecules such as CTLA4 and IL-10. Met inhibits the differentiation of naïve CD4+ T cells into inducible Treg (iTreg) by reducing forkhead box P3 (Foxp3) protein, caused by mTORC1 activation that was determined by the elevation of phosphorylated S6 (pS6), a downstream molecule of mTORC1...
November 2017: EBioMedicine
https://www.readbyqxmd.com/read/29050936/t%C3%AE-riii-is-induced-by-tcr-signaling-and-downregulated-in-foxp3-regulatory-t-cells
#9
Sandra Ortega-Francisco, Marisol de la Fuente-Granada, Evelyn K Alvarez Salazar, Lizbeth Airais Bolaños-Castro, Gabriela Fonseca-Camarillo, Roxana Olguin-Alor, Germán R Alemán-Muench, Fernando López-Casillas, Chander Raman, Eduardo A García-Zepeda, Gloria Soldevila
TGF-β type III receptor (TβRIII) is a co-receptor for TGFβ family members required for high-affinity binding of these ligands to their receptors, potentiating their cellular functions. TGF-βs, Bone Morphogenetic Proteins (BMP2/4) and Inhibins/Activins regulate different checkpoints during T cell differentiation. We have previously reported that TβRIII modulates T cell development by protecting developing thymocytes from apoptosis, however the role of this co-receptor in peripheral lymphocytes still remains elusive...
December 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29048538/improvement-of-foxp3-stability-through-cns2-demethylation-by-tet-enzyme-induction-and-activation
#10
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/28993609/transcription-factor-foxo1-is-essential-for-il-9-induction-in-t-helper-cells
#11
Sakshi Malik, Srikanth Sadhu, Srikanth Elesela, Ramendra Pati Pandey, Amanpreet Singh Chawla, Deepak Sharma, Lipsa Panda, Deepak Rathore, Balram Ghosh, Vineet Ahuja, Amit Awasthi
Interleukin 9 (IL-9)-producing helper T (Th9) cells have a crucial function in allergic inflammation, autoimmunity, immunity to extracellular pathogens and anti-tumor immune responses. In addition to Th9, Th2, Th17 and Foxp3(+) regulatory T (Treg) cells produce IL-9. A transcription factor that is critical for IL-9 induction in Th2, Th9 and Th17 cells has not been identified. Here we show that the forkhead family transcription factor Foxo1 is required for IL-9 induction in Th9 and Th17 cells. We further show that inhibition of AKT enhances IL-9 induction in Th9 cells while it reciprocally regulates IL-9 and IL-17 in Th17 cells via Foxo1...
October 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28951701/the-role-of-regulatory-t-cells-and-genes-involved-in-their-differentiation-in-pathogenesis-of-selected-inflammatory-and-neoplastic-skin-diseases-part-i-treg-properties-and-functions
#12
REVIEW
Bogusław Nedoszytko, Magdalena Lange, Małgorzata Sokołowska-Wojdyło, Joanna Renke, Piotr Trzonkowski, Michał Sobjanek, Aneta Szczerkowska-Dobosz, Marek Niedoszytko, Aleksandra Górska, Jan Romantowski, Jarosław Skokowski, Leszek Kalinowski, Roman Nowicki
Regulatory T cells (Treg) can be divided into two types: the natural cells (tTreg), which arise in the thymus, and the induced cells (iTreg), which are produced in peripheral tissues during immune response. The most recently published studies indicate that the supervisory functions of these cells are weakened in the pathogenesis of autoimmune and neoplastic diseases of the skin. This may be a result of the domination of other immune cells in the skin, such as Th1/Th17/Th22 and Tc1 type in psoriasis and Th2 in atopic dermatitis...
August 2017: Postȩpy Dermatologii i Alergologii
https://www.readbyqxmd.com/read/28881761/transcription-factor-c-rel-is-indispensable-for-generation-of-thymic-but-not-of-peripheral-foxp3-regulatory-t-cells
#13
Maik Luu, Elena Jenike, Niyati Vachharajani, Alexander Visekruna
The transcription factor c-Rel has been shown to be crucial for development of regulatory T cells (Tregs). Recent studies have reported that the expression of transcription factor Helios in Foxp3(+) Tregs correlates with thymic origin of these cells (tTregs). Notably, we found that only the Helios(+)Foxp3(+) Treg cell population was substantially reduced in c-Rel deficient mice. In contrast to a defective tTreg development, we observed an expansion of mucosal Tregs during the induction of acute colitis in rel(-/-) mice...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28783731/metabolic-control-of-th17-and-induced-treg-cell-balance-by-an-epigenetic-mechanism
#14
Tao Xu, Kelly M Stewart, Xiaohu Wang, Kai Liu, Min Xie, Jae Kyu Ryu, Ke Li, Tianhua Ma, Haixia Wang, Lu Ni, Saiyong Zhu, Nan Cao, Dongwei Zhu, Yu Zhang, Katerina Akassoglou, Chen Dong, Edward M Driggers, Sheng Ding
Metabolism has been shown to integrate with epigenetics and transcription to modulate cell fate and function. Beyond meeting the bioenergetic and biosynthetic demands of T-cell differentiation, whether metabolism might control T-cell fate by an epigenetic mechanism is unclear. Here, through the discovery and mechanistic characterization of a small molecule, (aminooxy)acetic acid, that reprograms the differentiation of T helper 17 (TH17) cells towards induced regulatory T (iTreg) cells, we show that increased transamination, mainly catalysed by GOT1, leads to increased levels of 2-hydroxyglutarate in differentiating TH17 cells...
August 10, 2017: Nature
https://www.readbyqxmd.com/read/28759565/low-doses-of-cholera-toxin-and-its-mediator-camp-induce-ctla-2-secretion-by-dendritic-cells-to-enhance-regulatory-t-cell-conversion
#15
Cinthia Silva-Vilches, Katrien Pletinckx, Miriam Lohnert, Vladimir Pavlovic, Diyaaeldin Ashour, Vini John, Emilia Vendelova, Susanne Kneitz, Jie Zhou, Rena Chen, Thomas Reinheckel, Thomas D Mueller, Jochen Bodem, Manfred B Lutz
Immature or semi-mature dendritic cells (DCs) represent tolerogenic maturation stages that can convert naive T cells into Foxp3+ induced regulatory T cells (iTreg). Here we found that murine bone marrow-derived DCs (BM-DCs) treated with cholera toxin (CT) matured by up-regulating MHC-II and costimulatory molecules using either high or low doses of CT (CThi, CTlo) or with cAMP, a known mediator CT signals. However, all three conditions also induced mRNA of both isoforms of the tolerogenic molecule cytotoxic T lymphocyte antigen 2 (CTLA-2α and CTLA-2β)...
2017: PloS One
https://www.readbyqxmd.com/read/28736999/regulatory-t-cell-subsets-in-peripheral-blood-of-celiac-disease-patients-and-tlr2-expression-correlation-with-oxidative-stress
#16
Sanjay Kumar, Sadhna Lal, Archana Bhatnagar
The study was carried out to study expression of Toll like receptors 2 (TLR2), natural/inducible Treg and Interferon-γ alongside oxidative stress and understand their significance in pediatric samples. Influence of oxidative stress on Celiac Disease was analysed by evaluating lipid peroxidation, reduced glutathione, Glutathione peroxidase, etc. A comparison was performed among CD patients, CD patients on gluten free diet (GFD), and healthy controls. Peripheral nTregs exhibited a similar pattern of reduced numbers in CD and GFD cases when compared to healthy controls...
October 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28733878/role-of-tgf-%C3%AE-in-self-peptide-regulation-of-autoimmunity
#17
REVIEW
Bhagirath Singh, Michael D Krawetz, Rachel M De Lima, Rinee Mukherjee, Pratibha Chaturvedi, Edwin Lee-Chan, Edward H Leiter, Kelly L Summers
Transforming growth factor (TGF)-β has been implicated in regulation of the immune system, including autoimmunity. We have found that TGF-β is readily produced by T cells following immunization with self-peptide epitopes that downregulate autoimmune responses in type 1 diabetes (T1D) prone nonobese diabetic (NOD) mice. These include multiple peptide epitopes derived from the islet β-cell antigens GAD65 (GAD65 p202-221, GAD65 p217-236), GAD67 (GAD67 p210-229, GAD67 p225-244), IGRP (IGRP p123-145, IGRP p195-214) and insulin B-chain (Ins...
July 21, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28732437/effect-of-microrna-21-transfection-on-in-vitro-differentiation-of-human-naive-cd4-t-cells-to-regulatory-t-cells
#18
Haideh Namdari, Mojgan Ghayedi, Jamshid Hadjati, Farhad Rezaei, Kurosh Kalantar, Parisa Rahimzadeh, Eisa Salehi
Regulatory T cells (Tregs) are important components of the immune system that modulate responses of other cells. These cells are involved in peripheral tolerance mechanisms, so defect in development and function of these cells can result in autoimmune disease. Increasing evidence supports the role of microRNAs-21 (miR-21) in the regulation of forkhead box P3 (Foxp3) expression in Tregs. We aimed to determine whether miR-21 transfection to naive CD4+ T cells can be useful in generation of iTregs in-vitro. We investigated in-vitro differentiation of miR-21-transfected naive CD4+ T cells to iTregs and compared these iTregs to cytokine-differentiated iTregs and control group...
June 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28729608/programmed-death-one-homolog-maintains-the-pool-size-of-regulatory-t-cells-by-promoting-their-differentiation-and-stability
#19
Qi Wang, Jianwei He, Dallas B Flies, Liqun Luo, Lieping Chen
Programmed death one homolog (PD-1H) is an immunoglobulin superfamily molecule and primarily acts as a coinhibitor in the initiation of T cell response to antigens. Here, we report that genetic ablation of PD-1H in mice blocks the differentiation of naive T cells to Foxp3(+) inducible Treg cells (iTreg) with a significant decrease of iTreg in lymphoid organs. This effect of PD-1H is highly specific for iTreg because both naturally generated iTreg in gut-related tissues and in vitro induced iTreg by TGF-β were decreased whereas the genesis of natural Treg (nTreg) remains normal...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710254/the-plasticity-and-stability-of-regulatory-t-cells-during-viral-induced-inflammatory-lesions
#20
Siddheshvar Bhela, Siva Karthik Varanasi, Ujjaldeep Jaggi, Sarah S Sloan, Naveen K Rajasagi, Barry T Rouse
Ocular infection with HSV causes a chronic T cell-mediated inflammatory lesion in the cornea. Lesion severity is affected by the balance of different CD4 T cell subsets, with greater severity occurring when the activity of regulatory T cells (Tregs) is compromised. In this study, fate-mapping mice were used to assess the stability of Treg function in ocular lesions. We show that cells that were once Foxp3(+) functional Tregs may lose Foxp3 and become Th1 cells that could contribute to lesion expression. The instability primarily occurred with IL-2R(lo) Tregs and was shown, in part, to be the consequence of exposure to IL-12...
August 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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