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Tregs OR regulatory T cells

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https://www.readbyqxmd.com/read/28934489/antisense-oligonucleotides-targeting-translation-inhibitory-elements-in-5-utrs-can-selectively-increase-protein-levels
#1
Xue-Hai Liang, Hong Sun, Wen Shen, Shiyu Wang, Joyee Yao, Michael T Migawa, Huynh-Hoa Bui, Sagar S Damle, Stan Riney, Mark J Graham, Rosanne M Crooke, Stanley T Crooke
A variety of diseases are caused by deficiencies in amounts or activity of key proteins. An approach that increases the amount of a specific protein might be of therapeutic benefit. We reasoned that translation could be specifically enhanced using trans-acting agents that counter the function of negative regulatory elements present in the 5' UTRs of some mRNAs. We recently showed that translation can be enhanced by antisense oligonucleotides (ASOs) that target upstream open reading frames. Here we report the amount of a protein can also be selectively increased using ASOs designed to hybridize to other translation inhibitory elements in 5' UTRs...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934122/invasion-of-dendritic-cells-macrophages-and-neutrophils-by-the-bordetella-adenylate-cyclase-toxin-a-subversive-move-to-fool-host-immunity
#2
REVIEW
Giorgio Fedele, Ilaria Schiavoni, Irena Adkins, Nela Klimova, Peter Sebo
Adenylate cyclase toxin (CyaA) is released in the course of B. pertussis infection in the host's respiratory tract in order to suppress its early innate and subsequent adaptive immune defense. CD11b-expressing dendritic cells (DC), macrophages and neutrophils are professional phagocytes and key players of the innate immune system that provide a first line of defense against invading pathogens. Recent findings revealed the capacity of B. pertussis CyaA to intoxicate DC with high concentrations of 3',5'-cyclic adenosine monophosphate (cAMP), which ultimately skews the host immune response towards the expansion of Th17 cells and regulatory T cells...
September 21, 2017: Toxins
https://www.readbyqxmd.com/read/28934113/sphingosine-1-phosphate-signaling-and-its-pharmacological-modulation-in-allogeneic-hematopoietic-stem-cell-transplantation
#3
REVIEW
Philip Smith, Catherine O'Sullivan, Peter Gergely
Allogeneic haemopoietic stem cell transplantation (HSCT) is increasingly used to treat haematological malignant diseases via the graft-versus-leukaemia (GvL) or graft-versus-tumour effects. Although improvements in infectious disease prophylaxis, immunosuppressive treatments, supportive care, and molecular based tissue typing have contributed to enhanced outcomes, acute graft-versus-host disease and other transplant related complications still contribute to high mortality and significantly limit the more widespread use of HSCT...
September 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28932640/co-delivery-of-the-nkt-agonist-%C3%AE-galactosylceramide-and-tumor-antigens-to-cross-priming-dendritic-cells-breaks-tolerance-to-self-antigens-and-promotes-antitumor-responses
#4
Reem Ghinnagow, Julie De Meester, Luis Javier Cruz, Caroline Aspord, Stéphanie Corgnac, Elodie Macho-Fernandez, Daphnée Soulard, Josette Fontaine, Laurence Chaperot, Julie Charles, Fabrice Soncin, Fathia Mami-Chouaib, Joel Plumas, Christelle Faveeuw, François Trottein
Vaccines designed to abrogate the tolerance of tumor self-antigens and amplify cytotoxic CD8(+) T cells (CTLs) have promise for the treatment of cancer. Type I natural killer (NKT) cells have attracted considerable interest in the cancer therapy field. In the current study, we have exploited the unique ability of NKT cells to serve as T-helper cells to license dendritic cells (DCs) for cross priming with the aim to generate efficient CTL antitumor responses. To this end, we designed a nanoparticle-based vaccine to target cross-priming DCs via the Clec9a endocytic pathway...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28931869/dermatophagoides-pteronyssinus-immunotherapy-changes-the-t-regulatory-cell-activity
#5
M Gonzalez, I Doña, F Palomares, P Campo, M J Rodriguez, C Rondon, F Gomez, T D Fernandez, J R Perkins, M M Escribese, M J Torres, C Mayorga
Subcutaneous specific immunotherapy (SCIT) has been shown to modify the Dermatophagoides pteronissinus (DP) allergic response, characterized by generation of Treg cells. However, studies have reported no changes in the proportion of Treg cells after immunotherapy, indicating that the effects may be due to modifications in their regulatory activities. We aimed to determine whether Tregs generated by DP-SCIT can switch the allergic response to tolerant and study the involvement of suppressive cytokines on it...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931834/mild-hypothermia-provides-treg-stability
#6
Marek- Trzonkowska Natalia, Piekarska Karolina, Filipowicz Natalia, Piotrowski Arkadiusz, Gucwa Magdalena, Vogt Katrin, Sawitzki Birgit, Siebert Janusz, Trzonkowski Piotr
Regulatory T cells (Tregs) play crucial role in maintenance of peripheral tolerance. Recent clinical trials confirmed safety and efficacy of Treg treatment of deleterious immune responses. However, Tregs lose their characteristic phenotype and suppressive potential during expansion ex vivo. Therefore, multiple research teams have been studding Treg biology in aim to improve their stability in vitro. In the current paper, we demonstrate that mild hypothermia of 33 °C induces robust proliferation of Tregs, preserves expression of FoxP3, CD25 and Helios, and prevents TSDR methylation during culture in vitro...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931830/circulating-mycobacterium-tuberculosis-dosr-latency-antigen-specific-polyfunctional-regulatory-il10-th17-cd4-t-cells-differentiate-latent-from-active-tuberculosis
#7
Srabanti Rakshit, Vasista Adiga, Soumya Nayak, Pravat Nalini Sahoo, Prabhat Kumar Sharma, Krista E van Meijgaarden, Anto Jesuraj Uk J, Chirag Dhar, George D Souza, Greg Finak, Stephen C De Rosa, Tom H M Ottenhoff, Annapurna Vyakarnam
The functional heterogeneity of T cell responses to diverse antigens expressed at different stages of Mycobacterium tuberculosis (Mtb) infection, in particular early secreted versus dormancy related latency antigens expressed later, that distinguish subjects with latent (LTBI), pulmonary (PTB) or extrapulmonary (EPTB) tuberculosis remains unclear. Here we show blood central memory CD4 T-cell responses specific to Mtb dormancy related (DosR) latency, but not classical immunodominant secretory antigens, to clearly differentiate LTBI from EPTB and PTB...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931816/tgf%C3%AE-r-signalling-controls-cd103-cd11b-dendritic-cell-development-in-the-intestine
#8
C C Bain, J Montgomery, C L Scott, J M Kel, M J H Girard-Madoux, L Martens, T F P Zangerle-Murray, J Ober-Blöbaum, D Lindenbergh-Kortleve, J N Samsom, S Henri, T Lawrence, Y Saeys, B Malissen, M Dalod, B E Clausen, A McI Mowat
CD103(+)CD11b(+) dendritic cells (DCs) are unique to the intestine, but the factors governing their differentiation are unclear. Here we show that transforming growth factor receptor 1 (TGFβR1) has an indispensable, cell intrinsic role in the development of these cells. Deletion of Tgfbr1 results in markedly fewer intestinal CD103(+)CD11b(+) DCs and a reciprocal increase in the CD103(-)CD11b(+) dendritic cell subset. Transcriptional profiling identifies markers that define the CD103(+)CD11b(+) DC lineage, including CD101, TREM1 and Siglec-F, and shows that the absence of CD103(+)CD11b(+) DCs in CD11c-Cre...
September 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28931653/combined-ox40l-and-mtor-blockade-controls-effector-t-cell-activation-while-preserving-treg-reconstitution-after-transplant
#9
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/28931462/paradoxical-development-of-polymyositis-like-autoimmunity-through-augmented-expression-of-autoimmune-regulator-aire
#10
Hitoshi Nishijima, Tatsuya Kajimoto, Yoshiki Matsuoka, Yasuhiro Mouri, Junko Morimoto, Minoru Matsumoto, Hiroshi Kawano, Yasuhiko Nishioka, Hisanori Uehara, Keisuke Izumi, Koichi Tsuneyama, Il-Mi Okazaki, Taku Okazaki, Kazuyoshi Hosomichi, Ayako Shiraki, Makoto Shibutani, Kunitoshi Mitsumori, Mitsuru Matsumoto
Autoimmunity is prevented by the function of the autoimmune regulator [AIRE (Aire in mice)], which promotes the expression of a wide variety of tissue-restricted antigens (TRAs) from medullary thymic epithelial cells (mTECs) and from a subset of peripheral antigen-presenting cells (APCs). We examined the effect of additive expression of human AIRE (huAIRE) in a model of autoimmune diabetes in NOD mice. Unexpectedly, we observed that mice expressing augmented AIRE/Aire developed muscle-specific autoimmunity associated with incomplete maturation of mTECs together with impaired expression of Aire-dependent TRAs...
September 17, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28930796/navigating-t-cell-immunometabolism-in-transplantation
#11
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/28930685/human-tissue-resident-memory-t-cells-are-defined-by-core-transcriptional-and-functional-signatures-in-lymphoid-and-mucosal-sites
#12
Brahma V Kumar, Wenji Ma, Michelle Miron, Tomer Granot, Rebecca S Guyer, Dustin J Carpenter, Takashi Senda, Xiaoyun Sun, Siu-Hong Ho, Harvey Lerner, Amy L Friedman, Yufeng Shen, Donna L Farber
Tissue-resident memory T cells (TRMs) in mice mediate optimal protective immunity to infection and vaccination, while in humans, the existence and properties of TRMs remain unclear. Here, we use a unique human tissue resource to determine whether human tissue memory T cells constitute a distinct subset in diverse mucosal and lymphoid tissues. We identify a core transcriptional profile within the CD69(+) subset of memory CD4(+) and CD8(+) T cells in lung and spleen that is distinct from that of CD69(-) TEM cells in tissues and circulation and defines human TRMs based on homology to the transcriptional profile of mouse CD8(+) TRMs...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28930662/the-kinase-mtorc1-promotes-the-generation-and-suppressive-function-of-follicular-regulatory-t-cells
#13
Lifan Xu, Qizhao Huang, Haoqiang Wang, Yaxing Hao, Qiang Bai, Jianjun Hu, Yiding Li, Pengcheng Wang, Xiangyu Chen, Ran He, Bingshou Li, Xia Yang, Tingting Zhao, Yanyan Zhang, Yifei Wang, Juanjuan Ou, Houjie Liang, Yuzhang Wu, Xinyuan Zhou, Lilin Ye
Follicular regulatory T (Tfr) cells differentiate from conventional regulatory T (Treg) cells and suppress excessive germinal center (GC) responses by acting on both GC B cells and T follicular helper (Tfh) cells. Here, we examined the impact of mTOR, a serine/threonine protein kinase that senses and integrates diverse environmental cues, on the differentiation and functional competency of Tfr cells in response to protein immunization or viral infection. By genetically deleting Rptor or Rictor, essential components for mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), respectively, we found that mTORC1 but not mTORC2 is essential for Tfr differentiation...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28930660/the-irf4-gene-regulatory-module-functions-as-a-read-write-integrator-to-dynamically-coordinate-t%C3%A2-helper-cell-fate
#14
Veena Krishnamoorthy, Sunil Kannanganat, Mark Maienschein-Cline, Sarah L Cook, Jianjun Chen, Neil Bahroos, Evelyn Sievert, Emily Corse, Anita Chong, Roger Sciammas
Transcriptional regulation during CD4(+) T cell fate decisions enables their differentiation into distinct states, guiding immune responses toward antibody production via Tfh cells or inflammation by Teff cells. Tfh-Teff cell fate commitment is regulated by mutual antagonism between the transcription factors Bcl6 and Blimp-1. Here we examined how T cell receptor (TCR) signals establish and arbitrate Bcl6-Blimp-1 counter-antagonism. We found that the TCR-signal-induced transcription factor Irf4 is essential for the differentiation of Bcl6-expressing Tfh and Blimp-1-expressing Teff cells...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28930659/group-1-innate-lymphoid-cell-lineage-identity-is-determined-by-a-cis-regulatory-element-marked-by-a-long-non-coding-rna
#15
Walter K Mowel, Sam J McCright, Jonathan J Kotzin, Magalie A Collet, Asli Uyar, Xin Chen, Alexandra DeLaney, Sean P Spencer, Anthony T Virtue, EnJun Yang, Alejandro Villarino, Makoto Kurachi, Margaret C Dunagin, Gretchen Harms Pritchard, Judith Stein, Cynthia Hughes, Diogo Fonseca-Pereira, Henrique Veiga-Fernandes, Arjun Raj, Taku Kambayashi, Igor E Brodsky, John J O'Shea, E John Wherry, Loyal A Goff, John L Rinn, Adam Williams, Richard A Flavell, Jorge Henao-Mejia
Commitment to the innate lymphoid cell (ILC) lineage is determined by Id2, a transcriptional regulator that antagonizes T and B cell-specific gene expression programs. Yet how Id2 expression is regulated in each ILC subset remains poorly understood. We identified a cis-regulatory element demarcated by a long non-coding RNA (lncRNA) that controls the function and lineage identity of group 1 ILCs, while being dispensable for early ILC development and homeostasis of ILC2s and ILC3s. The locus encoding this lncRNA, which we termed Rroid, directly interacted with the promoter of its neighboring gene, Id2, in group 1 ILCs...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28930651/driving-rel-iant-tregs-toward-an-identity-crisis
#16
Amy Li, Tyler Jacks
Inhibiting Treg cell function in tumors is an attractive strategy to improve anti-cancer immunity. In a pair of papers in Immunity and Cell, Ghosh and colleagues show that the canonical NF-κB subunits p65 and c-Rel have non-redundant, critical roles in promoting Treg cell development and function (Oh et al., 2017). Targeting c-Rel blunts Treg cell immunosuppressive activity in the tumor microenvironment and enhances anti-tumor T cell responses (Grinberg-Bleyer et al., 2017).
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28930556/osteoimmunology-the-nexus-between-bone-and-immune-system
#17
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/28930551/uremic-toxins-are-conditional-danger-or-homeostasis-associated-molecular-patterns
#18
Yu Sun, Candice Johnson, Jun Zhou, Luqiao Wang, Ya-Feng Li, Yifan Lu, Gayani Nanayakkara, Hangfei Fu, Ying Shao, Claudette Sanchez, William Y Yang, Xin Wang, Eric T Choi, Rongshan Li, Hong Wang, Xiao-Feng Yang
We mined novel uremic toxin (UT) metabolomics/gene databases, and analyzed the expression changes of UT receptors and UT synthases in chronic kidney disease (CKD) and cardiovascular disease (CVD). We made the following observations: 1) UTs represent only 1/80(th) of human serum small-molecule metabolome; 2) Some UTs are increased in CKD and CVD; 3) UTs either induce or suppress the expression of inflammatory molecules; 4) The expression of UT genes is significantly modulated in CKD patients, and coronary artery disease (CAD) patients; 5) The expression of UT genes is upregulated by caspase-1 and TNF-alpha pathways but is inhibited in regulatory T cells...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28930109/abcg2-regulatory-single-nucleotide-polymorphisms-alter-in-vivo-enhancer-activity-and-expression
#19
Rachel J Eclov, Mee J Kim, Aparna Chhibber, Robin P Smith, Nadav Ahituv, Deanna L Kroetz
OBJECTIVES: The expression and activity of the breast cancer resistance protein (ABCG2) contributes toward the pharmacokinetics of endogenous and xenobiotic substrates. The effect of genetic variation on the activity of cis-regulatory elements and nuclear response elements in the ABCG2 locus and their contribution toward ABCG2 expression have not been investigated systematically. In this study, the effect of genetic variation on the in-vitro and in-vivo enhancer activity of six previously identified liver enhancers in the ABCG2 locus was examined...
September 18, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28929578/horizontal-transfer-of-mir-23a-from-hypoxic-tumor-cell-colonies-can-induce-angiogenesis
#20
T V Sruthi, Lincy Edatt, Grace R Raji, Haritha K, S Sharath Shankar, Vandana Shankar, Vishnu R, Aswini P, V B Sameer Kumar
Neo vessel formation by angiogenesis is an important event during many pathological conditions including cancer, where it is indispensable for tumor growth and survival. Although, various pro-angiogenic cytokines and soluble factors, secreted by tumor cells, have been reported to promote angiogenesis, recent studies have shown regulatory role of exosomes, secreted by tumor cells in the process of angiogenesis. These exosomes are capable of carrying nucleic acids, proteins etc. as their cargo. Under the light of these facts and considering the presence of miRNAs, the non-coding RNAs capable of regulating target gene expression, as one of the major cargos in the exosomes, we investigated, whether exosomes derived from normoxic and hypoxic tumor cell colonies exhibit difference in levels of miR-23∼27∼24 cluster members and if so, to check the significance of their horizontall transfer on the process of angiogenesis...
September 20, 2017: Journal of Cellular Physiology
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