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Foxp3 transplant

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https://www.readbyqxmd.com/read/28643491/association-of-foxp3-polymorphism-with-allograft-outcome-in-kidney-transplantation
#1
Hyewon Park, Nuri Lee, Ji Won In, Eun Youn Roh, Kyoung Un Park, Sue Shin, Jaeseok Yang, Eun Young Song
BACKGROUND: Forkhead box P3 (Foxp3) is the most reliable marker for regulatory T cells, which play an important role in maintaining renal allograft tolerance. Recently, Foxp3 polymorphisms have been reported to be associated with graft outcome in kidney transplantation. We analyzed the association of Foxp3 polymorphisms with renal allograft outcome. METHODS: Foxp3 polymorphisms (rs3761548 A/C, rs2280883 C/T, rs5902434 del/ATT, and rs2232365 A/G) were tested by PCR with sequence-specific primers (PCR-SSP) in 231 adult kidney transplantation recipients from 1996-2004 at Seoul National University Hospital...
September 2017: Annals of Laboratory Medicine
https://www.readbyqxmd.com/read/28638744/azacytidine-prevents-experimental-xenogeneic-graft-versus-host-disease-without-abrogating-graft-versus-leukemia-effects
#2
Grégory Ehx, Gilles Fransolet, Laurence de Leval, Stéphanie D'Hondt, Sophie Lucas, Muriel Hannon, Loïc Delens, Sophie Dubois, Pierre Drion, Yves Beguin, Stéphanie Humblet-Baron, Frédéric Baron
The demethylating agent 5-azacytidine (AZA) has proven its efficacy in the treatment of myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading to the generation of regulatory T cells (Treg). Here, we investigated the impact of AZA on xenogeneic graft-vs.-host disease (xGVHD) and graft-vs.-leukemia effects in a humanized murine model of transplantation (human PBMCs-infused NSG mice), and described the impact of the drug on human T cells in vivo...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638110/a-novel-and-effective-method-to-generate-human-porcine-specific-regulatory-t-cells-with-high-expression-of-il-10-tgf-%C3%AE-1-and-il-35
#3
Mingqian Li, Judith Eckl, Christiane Geiger, Dolores J Schendel, Heike Pohla
Organ transplantation remains the most effective treatment for patients with late stage organ failure. Transgenic pigs provide an alternative organ donor source to the limited availability of human organs. However, cellular rejection still remains to be the obstacle for xenotransplantation. Superior to other methods, antigen-specific regulatory T cells (Treg) alleviate cellular rejection with fewer side effects. Here we demonstrate the use of a fast method to provide tolerogenic dendritic cells (tolDC) that can be used to generate effective porcine-specific Treg cells (PSTreg)...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637803/protein-malnutrition-alters-tryptophan-and-angiotensin-converting-enzyme-2-homeostasis-and-adaptive-immune-responses-in-human-rotavirus-infected-gnotobiotic-pigs-transplanted-with-human-infant-fecal-microbiota
#4
David D Fischer, Sukumar Kandasamy, Francine C Paim, Stephanie N Langel, Moyasar A Alhamo, Lulu Shao, Juliet Chepngeno, Ayako Miyazaki, Huang-Chi Huang, Anand Kumar, Gireesh Rajashekara, Linda J Saif, Anastasia N Vlasova
Malnutrition leads to increased morbidity and is evident in almost half of all deaths in children under the age of five. Mortality due to rotavirus diarrhea is common in developing countries where malnutrition is prevalent; however, the relationship between malnutrition and rotavirus infection remains unclear. In this study, gnotobiotic pigs transplanted with the fecal microbiota of a healthy 2-month-old infant were fed protein-sufficient or -deficient diets with infected with virulent human rotavirus. After human rotavirus infection, protein deficient pigs had decreased human rotavirus antibody titers and total IgA concentrations, systemic T helper (CD3+CD4+) and cytotoxic T (CD3+CD8+) lymphocyte frequencies and serum tryptophan and angiotensin I converting enzyme 2...
June 21, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28623282/a-nationwide-study-of-severe-and-protracted-diarrhoea-in-patients-with-primary-immunodeficiency-diseases
#5
Wen-I Lee, Chien-Chang Chen, Tang-Her Jaing, Liang-Shiou Ou, Chuen Hsueh, Jing-Long Huang
Diarrhoea lasting longer than 14 days and failing to respond to conventional management is defined as severe and protracted diarrhoea (SD). In this study, we investigated the prevalence, pathogens and prognosis of SD in primary immunodeficiency diseases (PIDs). Among 246 patients with predominantly paediatric-onset PIDs from 2003-2015, 21 [Btk (six), IL2RG (four), WASP, CD40L, gp91 (three each), gp47, RAG2 (one each)] and five [CVID (four), SCID (one)] without identified mutations had SD before prophylactic treatment...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28620237/lea29y-expression-in-transgenic-neonatal-porcine-islet-like-cluster-promotes-long-lasting-xenograft-survival-in-humanized-mice-without-immunosuppressive-therapy
#6
L Wolf-van Buerck, M Schuster, F S Oduncu, A Baehr, T Mayr, S Guethoff, J Abicht, B Reichart, N Klymiuk, E Wolf, J Seissler
Genetically engineered pigs are a promising source for islet cell transplantation in type 1 diabetes, but the strong human anti-pig immune response prevents its successful clinical application. Here we studied the efficacy of neonatal porcine islet-like cell clusters (NPICCs) overexpressing LEA29Y, a high-affinity variant of the T cell co-stimulation inhibitor CTLA-4Ig, to engraft and restore normoglycemia after transplantation into streptozotocin-diabetic NOD-SCID IL2rγ(-/-) (NSG) mice stably reconstituted with a human immune system...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28619045/human-adipose-derived-mesenchymal-stem-cells-alleviate-obliterative-bronchiolitis-in-a-murine-model-via-ido
#7
Guoping Zheng, Guanguan Qiu, Menghua Ge, Jianping He, Lanfang Huang, Ping Chen, Wei Wang, Qi Xu, Yaoqin Hu, Qiang Shu, Jianguo Xu
BACKGROUND: Long-term survival of lung transplantation is hindered by the development of obliterative bronchiolitis (OB). Adipose-derived stem cells (ASCs) were documented to have more potent immunosuppressive ability than mesenchymal stem cells (MSCs) from bone marrow and placenta. The goal of our study is to evaluate the effect of repeated administration of ASCs on OB and the involvement of indoleamine 2,3-dioxygenase (IDO) mediating the protective effect of ASCs in a heterotopic tracheal transplantation (HTT) model...
June 15, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28608637/regulatory-t-cell-therapy-in-liver-transplantation
#8
REVIEW
Gavin P Whitehouse, Andrew Hope, Alberto Sanchez-Fueyo
Modern immunosuppression drug regimens have produced excellent short term survival after liver transplantation but it is generally accepted that the side effects of these medications remain a significant contributing factor for less satisfactory long term outcomes. The liver has unique tolerogenic properties as evidenced by the higher rates of operational tolerance seen in liver transplant recipients compared to other solid organ transplants and therefore liver transplantation offers an attractive setting in which to study tolerising therapies...
June 13, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28600182/mesenchymal-stem-cells-can-induce-regulatory-t-cells-via-modulating-mir-126a-but-not-mir-10a
#9
Maryam Khosravi, Mohammad Hossein Karimi, Mahdokht Hossein Aghdaie, Mehdi Kalani, Sina Naserian, Ali Bidmeshkipour
Among the different immunosuppressive properties attributed to mesenchymal stem cells (MSCs), one relies on their ability to induce regulatory T cells (iTregs) from conventional T cells under particular inflammatory context. Stable Foxp3 expression plays a major role in the phenotypic and functional stability of iTregs. However, the mechanism behind Foxp3 induction in iTregs by MSCs remains unknown. Here, we assessed the possible effect of MSCs on miR-126a and miR-10a expression in iTregs and, consequently on Foxp3 stability, a regulatory pathway that has not yet been explored...
June 18, 2017: Gene
https://www.readbyqxmd.com/read/28590550/osi-027-modulates-acute-graft-versus-host-disease-after-liver-transplantation-in-a-rat-model
#10
Xiao Zhi, Fei Xue, Wei Chen, Chao Liang, Hao Liu, Tao Ma, Xuefeng Xia, Liqiang Hu, Xueli Bai, Tingbo Liang
Despite its rarity (1%-2%), acute graft-versus-host disease after liver transplantation (LTx-aGVHD) has a high mortality rate (85%). A gradual decrease in regulatory T cells (T-regs) correlates with disease progression in a rat LTx-GVHD model and treatments which increase T-regs exert therapeutic effects on LTx-aGVHD. In this study, LTx-aGVHD model rats were treated with rapamycin (RAPA), OSI-027 or an equal quantity of vehicle. Rats treated with OSI-027 survived longer (>100 days) than those in the RAPA (70±8 days) or control (24±3 days) groups...
June 7, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28584086/il-2-therapy-restores-regulatory-t-cell-dysfunction-induced-by-calcineurin-inhibitors
#11
Gavin Whitehouse, Elizabeth Gray, Sotiris Mastoridis, Elliot Merritt, Elisavet Kodela, Jennie H M Yang, Richard Danger, Marta Mairal, Sofia Christakoudi, Juan J Lozano, Iain C Macdougall, Timothy I M Tree, Alberto Sanchez-Fueyo, Marc Martinez-Llordella
CD4(+)CD25(+)FOXP3(+) Tregs constitute a heterogeneous lymphocyte subpopulation essential for curtailing effector T cells and establishing peripheral tolerance. Calcineurin inhibitors (CNIs) are among the most effective agents in controlling effector T-cell responses in humans. However, CNIs also reduce the size of the Treg pool. The functional consequences of this negative effect and the mechanisms responsible remain to be elucidated. We report here that CNIs compromise the overall Treg immunoregulatory capacity to a greater extent than would be predicted by the reduction in the size of the Treg compartment, given that they selectively promote the apoptosis of the resting and activated Treg subsets that are known to display the most powerful suppressive function...
June 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28562677/correction-helios-expression-and-foxp3-tsdr-methylation-of-ifny-and-ifny-treg-from-kidney-transplant-recipients-with-good-long-term-graft-function
#12
Karina Trojan, Christian Unterrainer, Rolf Weimer, Nuray Bulut, Christian Morath, Mostafa Aly, Li Zhu, Gerhard Opelz, Volker Daniel
[This corrects the article DOI: 10.1371/journal.pone.0173773.].
2017: PloS One
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/28539427/tlr-induced-murine-dendritic-cell-dc-activation-requires-dc-intrinsic-complement
#14
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/28536366/advances-in-the-use-of-regulatory-t-cells-for-the-prevention-and-therapy-of-graft-vs-host-disease
#15
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/28508176/the-prognostic-role-of-cd68-and-foxp3-expression-in-patients-with-primary-central-nervous-system-lymphoma
#16
Hyunsoo Cho, Se Hoon Kim, Soo-Jeong Kim, Jong Hee Chang, Woo Ick Yang, Chang-Ok Suh, June-Won Cheong, Yu Ri Kim, Jung Yeon Lee, Ji Eun Jang, Yundeok Kim, Yoo Hong Min, Jin Seok Kim
The prognostic role of CD68 and FoxP3 in primary central nervous system lymphoma (PCNSL) has not been evaluated. Thus, we examined the prognostic significance of CD68 and FoxP3 expression in tumor samples of 76 newly diagnosed immunocompetent PCNSL patients. All patients were treated initially with high-dose methotrexate (HD-MTX)-based chemotherapy, and 16 (21.1%) patients received upfront autologous stem cell transplantation (ASCT) consolidation. High expression of CD68 (>55 cells/high-power field) or FoxP3 (>15 cells/high-power field) was observed in 10 patients, respectively...
July 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28506261/a-possible-role-of-low-regulatory-t-cells-in-anti-acetylcholine-receptor-antibody-positive-myasthenia-gravis-after-bone-marrow-transplantation
#17
Masahiko Fukatsu, Takenobu Murakami, Hiroshi Ohkawara, Shunichi Saito, Kazuhiko Ikeda, Suguru Kadowaki, Itaru Sasaki, Mari Segawa, Tomoko Soeda, Akihiko Hoshi, Hiroshi Takahashi, Akiko Shichishima-Nakamura, Kazuei Ogawa, Yoshihiro Sugiura, Hitoshi Ohto, Yasuchika Takeishi, Takayuki Ikezoe, Yoshikazu Ugawa
BACKGROUND: Chronic graft-versus-host disease (GVHD) appears several months following allogenic hematopoietic stem cell transplantation (HSCT) and is clinically analogous to autoimmune disorder. Polymyositis is a common neuromuscular disorder in chronic GVHD, but myasthenia gravis (MG) is extremely rare. Hence, its pathophysiology and treatment have not been elucidated. CASE PRESENTATION: A 63-year-old man with a history of chronic GVHD presented with ptosis, dropped head, and dyspnea on exertion, which had worsened over the previous several months...
May 15, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28485401/foxp3-regulatory-t-cells-maintain-the-bone-marrow-microenvironment-for-b-cell-lymphopoiesis
#18
Antonio Pierini, Hidekazu Nishikii, Jeanette Baker, Takaharu Kimura, Hye-Sook Kwon, Yuqiong Pan, Yan Chen, Maite Alvarez, William Strober, Andrea Velardi, Judith A Shizuru, Joy Y Wu, Shigeru Chiba, Robert S Negrin
Foxp3(+) regulatory T cells (Treg cells) modulate the immune system and maintain self-tolerance, but whether they affect haematopoiesis or haematopoietic stem cell (HSC)-mediated reconstitution after transplantation is unclear. Here we show that B-cell lymphopoiesis is impaired in Treg-depleted mice, yet this reduced B-cell lymphopoiesis is rescued by adoptive transfer of affected HSCs or bone marrow cells into Treg-competent recipients. B-cell reconstitution is abrogated in both syngeneic and allogeneic transplantation using Treg-depleted mice as recipients...
May 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28484247/total-fecal-microbiota-transplantation-alleviates-high-fat-diet-induced-steatohepatitis-in-mice-via-beneficial-regulation-of-gut-microbiota
#19
Da Zhou, Qin Pan, Feng Shen, Hai-Xia Cao, Wen-Jin Ding, Yuan-Wen Chen, Jian-Gao Fan
Non-alcoholic steatohepatitis (NASH) is an epidemic metabolic disease with limited therapeutic strategies. Cumulative data support the pivotal role of gut microbiota in NASH. Here, we investigated the hypothesis regarding whether fecal microbiota transplantation (FMT) is effective in attenuating high-fat diet (HFD)-induced steatohepatitis in mice. Mice were randomized into control, HFD and HFD + FMT groups. After an 8-week HFD, FMT treatment was initiated and carried out for 8 weeks. The gut microbiota structure, butyrate concentrations of the cecal content, liver pathology and intrahepatic lipid and cytokines were examined...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28474504/mouse-nidovirus-ldv-infection-alleviates-graft-versus-host-disease-and-induces-type-i-ifn-dependent-inhibition-of-dendritic-cells-and-allo-responsive-t-cells
#20
Mélanie Gaignage, Reece G Marillier, Catherine Uyttenhove, Nicolas Dauguet, Anubha Saxena, Bernard Ryffel, Thomas Michiels, Jean-Paul Coutelier, Jacques Van Snick
INTRODUCTION: Viruses have developed multiple mechanisms to alter immune reactions. In 1969, it was reported that lactate dehydrogenase-elevating virus (LDV), a single stranded positive sense mouse nidovirus, delays skin allograft rejection and inhibits spleen alterations in graft versus host disease (GVHD). As the underlying mechanisms have remained unresolved and given the need for new therapies of this disease, we reassessed the effects of the virus on GVHD and tried to uncover its mode of action...
June 2017: Immunity, Inflammation and Disease
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