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Regulatory B cell in transplantation

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https://www.readbyqxmd.com/read/28738016/eomesodermin-promotes-the-development-of-type-1-regulatory-t-tr1-cells
#1
Ping Zhang, Jason S Lee, Kate H Gartlan, Iona S Schuster, Iain Comerford, Antiopi Varelias, Md Ashik Ullah, Slavica Vuckovic, Motoko Koyama, Rachel D Kuns, Kelly R Locke, Kirrilee J Beckett, Stuart D Olver, Luke D Samson, Marcela Montes de Oca, Fabian de Labastida Rivera, Andrew D Clouston, Gabrielle T Belz, Bruce R Blazar, Kelli P MacDonald, Shaun R McColl, Ranjeny Thomas, Christian R Engwerda, Mariapia A Degli-Esposti, Axel Kallies, Siok-Keen Tey, Geoffrey R Hill
Type 1 regulatory T (TR1) cells are Foxp3(-) interleukin-10 (IL-10)-producing CD4(+) T cells with potent immunosuppressive properties, but their requirements for lineage development have remained elusive. We show that TR1 cells constitute the most abundant regulatory population after allogeneic bone marrow transplantation (BMT), express the transcription factor Eomesodermin (Eomes), and are critical for the prevention of graft-versus-host disease. We demonstrate that Eomes is required for TR1 cell differentiation, during which it acts in concert with the transcription factor B lymphocyte-induced maturation protein-1 (Blimp-1) by transcriptionally activating IL-10 expression and repressing differentiation into other T helper cell lineages...
April 7, 2017: Science Immunology
https://www.readbyqxmd.com/read/28736026/yogurt-feeding-induced-the-prolongation-of-fully-major-histocompatibility-complex-mismatched-murine-cardiac-graft-survival-by-induction-of-cd4-foxp3-cells
#2
M Uchiyama, E Yin, T Yanagisawa, X Jin, M Hara, S Matsuyama, T Imazuru, K Uchida, M Kawamura, M Niimi
Yogurt is a nutrient-rich food and the beneficial effects of yogurt on both health and immunomodulatory effects are well documented. In this pilot study, we investigated the effects of commercially produced yogurt R-1 on alloimmune responses in a murine cardiac transplantation model. The R-1 is produced by Meiji Co., Ltd., and contains live and active lactic acid bacteria (lactobacillus bulgaricus OLL1073R-1) mainly. CBA (H2(k)) mice underwent transplantation of a C57BL/6 (H2(b); B6) heart and received oral administration of 1 mL, 0...
July 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28698955/role-of-natural-igm-autoantibodies-igm-naa-and-igm-anti-leukocyte-antibodies-igm-ala-in-regulating-inflammation
#3
Peter I Lobo
Natural IgM autoantibodies (IgM-NAA) are rapidly produced to inhibit pathogens and abrogate inflammation mediated by invading microorganisms and host neoantigens. IgM-NAA achieve this difficult task by being polyreactive with low binding affinity but with high avidity, characteristics that allow these antibodies to bind antigenic determinants shared by pathogens and neoantigens. Hence the same clones of natural IgM can bind and mask host neoantigens as well as inhibit microorganisms. In addition, IgM-NAA regulate the inflammatory response via mechanisms involving binding of IgM to apoptotic cells to enhance their removal and binding of IgM to live leukocytes to regulate their function...
July 12, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28698304/prediction-of-clinically-relevant-herb-drug-clearance-interactions-using-a-whole-cell-approach-schisandra-sphenanthera-case-study
#4
Jonathan P Jackson, Kimberly M Freeman, Weslyn W Friley, Ashley G Herman, Christopher B Black, Kenneth R Brouwer, Amy L Roe
The Schisandraceae family is reported to have a range of pharmacological activities, including anti-inflammatory effects. As with all herbal preparations, extracts of Schisandra species are mixtures composed of >50 lignans including schizandrins and deoxyschizandrins. In China, Schisandra sphenanthera extract (SSE) is often co-administered with immunosuppressant treatment of transplant recipients. In cases of co-administration, the potential for herb-drug interactions (HDI) increases. Clinical studies have been employed to assess HDI of extracts including SSE...
July 11, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28638744/azacytidine-prevents-experimental-xenogeneic-graft-versus-host-disease-without-abrogating-graft-versus-leukemia-effects
#5
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/28637621/gata2-deficiency-and-related-myeloid-neoplasms
#6
Marcin W Wlodarski, Matthew Collin, Marshall S Horwitz
The GATA2 gene codes for a hematopoietic transcription factor that through its two zinc fingers (ZF) can occupy GATA-DNA motifs in a countless number of genes. It is crucial for the proliferation and maintenance of hematopoietic stem cells. During the past 5 years, germline heterozygous mutations in GATA2 were reported in several hundred patients with various phenotypes ranging from mild cytopenia to severe immunodeficiency involving B cells, natural killer cells, CD4(+) cells, monocytes and dendritic cells (MonoMAC/DCML), and myeloid neoplasia...
April 2017: Seminars in Hematology
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
#7
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/28615039/interleukin-21-promotes-thymopoiesis-recovery-following-hematopoietic-stem-cell-transplantation
#8
Aurélie Tormo, Fatemeh Khodayarian, Yun Cui, Edouard Al-Chami, Reem Kanjarawi, Beatriz Noé, Huijie Wang, Moutih Rafei
BACKGROUND: Impaired T cell reconstitution remains a major deterrent in the field of bone marrow (BM) transplantation (BMT) due to pre-conditioning-induced damages inflicted to the thymi of recipient hosts. Given the previously reported thymo-stimulatory property of interleukin (IL)-21, we reasoned that its use post-BMT could have a profound effect on de novo T cell development. METHODS: To evaluate the effect of IL-21 on de novo T cell development in vivo, BM derived from RAG2p-GFP mice was transplanted into LP/J mice...
June 14, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28607754/lymphocyte-reconstitution-following-autologous-stem-cell-transplantation-for-progressive-ms
#9
G Cull, D Hall, M J Fabis-Pedrini, W M Carroll, L Forster, F Robins, R Ghassemifar, C Crosbie, S Walters, I James, B Augustson, A K Kermode
BACKGROUND: Autologous stem cell transplantation (ASCT) for progressive multiple sclerosis (MS) may reset the immune repertoire. OBJECTIVE: The objective of this paper is to analyse lymphocyte recovery in patients with progressive MS treated with ASCT. METHODS: Patients with progressive MS not responding to conventional treatment underwent ASCT following conditioning with high-dose cyclophosphamide and antithymocyte globulin. Lymphocyte subset analysis was performed before ASCT and for two years following ASCT...
January 2017: Multiple Sclerosis Journal—Experimental, Translational and Clinical
https://www.readbyqxmd.com/read/28572052/hematopoietic-stem-cell-transplantation-in-autoimmune-disorders-from-immune-regulatory-processes-to-clinical-implications
#10
REVIEW
Margit Zeher, Gábor Papp, Britt Nakken, Peter Szodoray
Autoimmune diseases are characterized by the development of autoreactive T- and B-cells targeting self-antigens, which eventually can result in chronic and persistent organ damage. The autologous hematopoietic stem cell transplantation (AHSCT) opened new avenues in the treatment of patients with severe, treatment-resistant autoimmune diseases. This paper reviews the immune-regulatory mechanisms behind AHSCT, and also summarizes the experiences of clinical practice related to the therapy in organ-specific and systemic autoimmune diseases...
May 29, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28546003/thymic-epithelial-cell-specific-deletion-of-jmjd6-reduces-aire-protein-expression-and-exacerbates-disease-development-in-a-mouse-model-of-autoimmune-diabetes
#11
Toyoshi Yanagihara, Takahiro Tomino, Takehito Uruno, Yoshinori Fukui
Thymic epithelial cells (TECs) establish spatially distinct microenvironments in which developing T cells are selected to mature or die. A unique property of medullary TECs is their expression of thousands of tissue-restricted self-antigens that is largely under the control of the transcriptional regulator Aire. We previously showed that Jmjd6, a lysyl hydroxylase for splicing regulatory proteins, is important for Aire protein expression and that transplantation of Jmjd6-deficient thymic stroma into athymic nude mice resulted in multiorgan autoimmunity...
July 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28534310/combination-immunotherapy-for-type-1-diabetes
#12
REVIEW
Robert N Bone, Carmella Evans-Molina
PURPOSE OF REVIEW: Type 1 diabetes (T1D) is an autoimmune disease marked by β-cell destruction. Immunotherapies for T1D have been investigated since the 1980s and have focused on restoration of tolerance, T cell or B cell inhibition, regulatory T cell (Treg) induction, suppression of innate immunity and inflammation, immune system reset, and islet transplantation. The purpose of this review is to provide an overview and lessons learned from single immunotherapy trials, describe recent and ongoing combination immunotherapy trials, and provide perspectives on strategies for future combination clinical interventions aimed at preserving insulin secretion in T1D...
July 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28529840/adoptive-cell-therapy-with-tregs-to-improve-transplant-outcomes-the-promise-and-the-stumbling-blocks
#13
Mohamed B Ezzelarab, Angus W Thomson
The contribution of regulatory T cells (Treg) to the induction and maintenance of tolerance is well-recognized in rodents and may contribute to long-term human organ allograft survival. The therapeutic efficacy of adoptively-transferred Treg in promoting tolerance to organ allografts is well-recognized in mouse models. Early phase 1/2 clinical studies of Treg therapy have been conducted in patients with type-1 (autoimmune) diabetes and refractory Crohn's disease, and for inhibition of graft-versus-host disease following bone marrow transplantation with proven safety...
December 2016: Current Transplantation Reports
https://www.readbyqxmd.com/read/28485401/foxp3-regulatory-t-cells-maintain-the-bone-marrow-microenvironment-for-b-cell-lymphopoiesis
#14
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/28484450/il-2-mediated-in-vivo-expansion-of-regulatory-t-cells-combined-with-cd154-cd40-co-stimulation-blockade-but-not-ctla-4-ig-prolongs-allograft-survival-in-naive-and-sensitized-mice
#15
Lerisa Govender, Jean-Christophe Wyss, Rajesh Kumar, Manuel Pascual, Dela Golshayan
In recent years, regulatory T cells (Treg)-based immunotherapy has emerged as a promising strategy to promote operational tolerance after solid organ transplantation (SOT). However, a main hurdle for the therapeutic use of Treg in transplantation is their low frequency, particularly in non-lymphopenic hosts. We aimed to expand Treg directly in vivo and determine their efficacy in promoting donor-specific tolerance, using a stringent experimental model. Administration of the IL-2/JES6-1 immune complex at the time of transplantation resulted in significant expansion of donor-specific Treg, which suppressed alloreactive T cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28470865/assessing-the-impact-of-foxp3-and-vav1-gene-polymorphisms-on-kidney-allograft-survival
#16
M Adamek, B Döhler, K K Hasan, G Fiedler, S Scherer, G Opelz, T H Tran
FoxP3 and Vav1 are known to be involved in the development of regulatory T cells. Two polymorphic sites in the FoxP3 promoter (rs3761548 and a (GT) n -dinucleotide repeat) and 2 single nucleotide polymorphisms in intron 1 of the Vav1 gene (rs2546133 and rs2617822) have been shown to correlate with gene expression levels. We investigated a potential impact of FoxP3 and Vav1 genetic variants on kidney allograft failure using samples and data of the Collaborative Transplant Study. A cohort of 384 kidney transplant patients was tested...
May 3, 2017: HLA
https://www.readbyqxmd.com/read/28470464/expanding-diversity-and-common-goal-of-regulatory-t-and-b-cells-ii-in-allergy-malignancy-and-transplantation
#17
REVIEW
Grażyna Korczak-Kowalska, Anna Stelmaszczyk-Emmel, Katarzyna Bocian, Ewelina Kiernozek, Nadzieja Drela, Joanna Domagała-Kulawik
Regulation of immune response was found to play an important role in the course of many diseases such as autoimmune diseases, allergy, malignancy, organ transplantation. The studies on immune regulation focus on the role of regulatory cells (Tregs, Bregs, regulatory myeloid cells) in these disorders. The number and function of Tregs may serve as a marker of disease activity. As in allergy, the depletion of Tregs is observed and the results of allergen-specific immunotherapy could be measured by an increase in the population of IL-10(+) regulatory cells...
May 3, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28465534/low-proportion-of-follicular-regulatory-t-cell-in-renal-transplant-patients-with-chronic-antibody-mediated-rejection
#18
Wen Chen, Jian Bai, Haiyan Huang, Lili Bi, Xiangrui Kong, Yu Gao, Yong Han, Li Xiao, Bingyi Shi
Follicular regulatory T (Tfr) cell can effectively regulate humoral immunity, but its function and mechanism in antibody-mediated rejection (AMR) after organ transplantation remains unclear. Here we detected follicular helper T (Tfh) cell subsets in 88 renal transplant patients with chronic renal allograft dysfunction (40 with AMR and 48 without AMR). The ratio of Tfr cells in renal graft tissues and peripheral blood of AMR patients significantly decreased, while the ratio of IL-21-producing Tfh cells (Tfh2 and Tfh17) significantly increased, compared to non-AMR patients...
May 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28461110/granzyme-b-producing-b-cells-in-renal-transplant-patients
#19
Jiqiao Zhu, Ye Zeng, Sebastian Dolff, Anja Bienholz, Monika Lindemann, Alexandra Brinkhoff, Manfred Schedlowski, Shilei Xu, Ming Sun, Hana Guberina, Julia Kirchhof, Andreas Kribben, Oliver Witzke, Benjamin Wilde
OBJECTIVES: A separate subset of Granzyme B (GrB) producing B-cells regulating T-cell mediated immunity has been identified. In the present study, we investigated the role of GrB(+) B-cells in renal transplant patients (RTX). METHODS: 12 healthy controls (HC) and 26 RTX patients were enrolled. In addition, 19 healthy volunteers treated with cyclosporine A (CsA) were enrolled. GrB(+) B-cells were determined via flow cytometry. RESULTS: RTX Patients showed a diminished fraction of GrB(+) B-cells as compared to HC...
April 28, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28434942/ipsc-derived-regulatory-dendritic-cells-inhibit-allograft-rejection-by%C3%A2-generating-alloantigen-specific-regulatory-t-cells
#20
Songjie Cai, Jiangang Hou, Masayuki Fujino, Qi Zhang, Naotsugu Ichimaru, Shiro Takahara, Ryoko Araki, Lina Lu, Ji-Mei Chen, Jian Zhuang, Ping Zhu, Xiao-Kang Li
Regulatory dendritic cell (DCregs)-based immunotherapy is a potential therapeutic tool for transplant rejection. We generated DCregs from murine induced pluripotent stem cells (iPSCs), which could remain in a "stable immature stage" even under strong stimulation. Harnessing this characteristic, we hypothesized that iPS-DCregs worked as a negative vaccine to generate regulatory T cells (Tregs), and induced donor-specific allograft acceptance. We immunized naive CBA (H-2K(k)) mice with B6 (H-2K(b)) iPS-DCregs and found that Tregs (CD4(+)CD25(+)FOXP3(+)) significantly increased in CBA splenocytes...
May 9, 2017: Stem Cell Reports
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