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Regulatory B cell in transplantation

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https://www.readbyqxmd.com/read/28935847/cd56bright-nk-regulatory-cells-in-filgrastim-primed-donor-blood-or-marrow-products-regulate-chronic-gvhd-cbmtg-randomized-0601-study-results
#1
Amina Kariminia, Sabine Ivison, Bernard Ng, Jacob Rozmus, Susanna Sung, Avani Varshney, Mahmoud Aljurf, Silvy Lachance, Irwin Walker, Cindy Toze, Jeff Lipton, Stephanie J Lee, Jeff Szer, Richard Doocey, Ian Lewis, Clayton Smith, Naeen Chaudhri, Megan K Levings, Raewyn Broady, Gerald Devins, David Szwajcer, Ronan Foley, Sara Mostafavi, Steven Pavletic, Donna A Wall, Stephen Couban, Tony Panzarella, Kirk R Schultz
Randomized trials have conclusively shown higher rates of chronic graft-versus-host disease with filgrastim-stimulated apheresis peripheral blood as a donor source than unstimulated bone marrow. The Canadian Blood and Marrow Transplant Group conducted a phase 3 study of adults who received either filgrastim-stimulated apheresis peripheral blood or filgrastim-stimulated bone marrow from human leukocyte antigen-identical sibling donors. Because all donors received the identical filgrastim dosing schedule, this study allowed for a controlled evaluation of the impact of stem cell source on development of chronic graft-versus-host disease...
September 21, 2017: Haematologica
https://www.readbyqxmd.com/read/28935578/abin1-determines-severity-of-glomerulonephritis-via-activation-of-intrinsic-glomerular-inflammation
#2
Erik A Korte, Dawn J Caster, Michelle T Barati, Min Tan, Shirong Zheng, Celine C Berthier, Frank C Brosius, Mark B Vieyra, Ryan M Sheehan, Michele Kosiewicz, Marcin Wysoczynski, Patrick M Gaffney, David J Salant, Kenneth R McLeish, David W Powell
Transcription factor NF-κB regulates expression of numerous genes that control inflammation and is activated in glomerular cells in glomerulonephritis (GN). We previously identified genetic variants for a NF-κB regulatory, ubiquitin binding protein ABIN1 as risk factors for GN in systemic autoimmunity. The goal here was to define glomerular inflammatory events controlled by ABIN1 function in GN. Nephrotoxic serum nephritis was induced in wild-type (WT) and ubiquitin binding deficient ABIN1[D485N] mice; and renal pathophysiology and glomerular inflammatory phenotypes were assessed...
September 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28931653/combined-ox40l-and-mtor-blockade-controls-effector-t-cell-activation-while-preserving-treg-reconstitution-after-transplant
#3
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/28928775/assessment-of-safety-and-functional-efficacy-of-stem-cell-based-therapeutic-approaches-using-retinal-degenerative-animal-models
#4
REVIEW
Tai-Chi Lin, Magdalene J Seiler, Danhong Zhu, Paulo Falabella, David R Hinton, Dennis O Clegg, Mark S Humayun, Biju B Thomas
Dysfunction and death of retinal pigment epithelium (RPE) and or photoreceptors can lead to irreversible vision loss. The eye represents an ideal microenvironment for stem cell-based therapy. It is considered an "immune privileged" site, and the number of cells needed for therapy is relatively low for the area of focused vision (macula). Further, surgical placement of stem cell-derived grafts (RPE, retinal progenitors, and photoreceptor precursors) into the vitreous cavity or subretinal space has been well established...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28898976/regulation-of-immune-and-neural-function-via-leukocyte-ig-like-receptors
#5
Kazuya Takeda, Akira Nakamura
Leukocyte Ig-like receptors (LILRs)/Ig-like transcripts (ILTs) are expressed on innate and adaptive immune cells and maintain immune homeostasis. LILRs consist of activating and inhibitory-type receptors that regulate adequate cellular functions. LILRs were firstly identified as MHC class I receptors, therefore expression and/or polymorphisms of LILRs are reported to associate with autoimmune disorders and transplant rejection; however, recent accumulating evidences have revealed that LILRs recognize with diverse ligands including bacteria and virus...
August 1, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28894451/inflammatory-conditions-dictate-the-effect-of-mesenchymal-stem-or-stromal-cells-on-b-cell-function
#6
Franka Luk, Laura Carreras-Planella, Sander S Korevaar, Samantha F H de Witte, Francesc E Borràs, Michiel G H Betjes, Carla C Baan, Martin J Hoogduijn, Marcella Franquesa
The immunomodulatory capacity of mesenchymal stem or stromal cells (MSC) makes them a promising tool for treatment of immune disease and organ transplantation. The effects of MSC on B cells are characterized by an abrogation of plasmablast formation and induction of regulatory B cells (Bregs). It is, however, unknown how MSC interact with B cells under inflammatory conditions. In this study, adipose tissue-derived MSC were pretreated with 50 ng/ml IFN-γ for 96 h (MSC-IFN-γ) to simulate inflammatory conditions...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28878768/natural-igm-and-tlr-agonists-switch-murine-splenic-pan-b-to-regulatory-cells-that-suppress-ischemia-induced-innate-inflammation-via-regulating-nkt-1-cells
#7
Peter I Lobo, Kailo H Schlegel, Amandeep Bajwa, Liping Huang, Mark D Okusa
Natural IgM anti-leukocyte autoantibodies (IgM-ALAs) inhibit inflammation by several mechanisms. Here, we show that pan-B cells and bone marrow-derived dendritic cells (BMDCs) are switched to regulatory cells when pretreated ex vivo with IgM. B cells are also switched to regulatory cells when pretreated ex vivo with CpG but not with LPS. Pre-emptive infusion of such ex vivo induced regulatory cells protects C57BL/6 mice from ischemia-induced acute kidney injury (AKI) via regulation of in vivo NKT-1 cells, which normally amplify the innate inflammatory response to DAMPS released after reperfusion of the ischemic kidney...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28878331/the-immunosuppressive-effect-of-the-tick-protein-salp15-is-long-lasting-and-persists-in-a-murine-model-of-hematopoietic-transplant
#8
Julen Tomás-Cortázar, Itziar Martín-Ruiz, Diego Barriales, Miguel Ángel Pascual-Itoiz, Virginia Gutiérrez de Juan, Alfredo Caro-Maldonado, Nekane Merino, Alberto Marina, Francisco J Blanco, Juana María Flores, James D Sutherland, Rosa Barrio, Adriana Rojas, María Luz Martínez-Chantar, Arkaitz Carracedo, Carolina Simó, Virginia García-Cañas, Leticia Abecia, José Luis Lavín, Ana M Aransay, Héctor Rodríguez, Juan Anguita
Salp15, a salivary protein of Ixodes ticks, inhibits the activation of naïve CD4 T cells. Treatment with Salp15 results in the inhibition of early signaling events and the production of the autocrine growth factor, interleukin-2. The fate of the CD4 T cells activated in the presence of Salp15 or its long-term effects are, however, unknown. We now show that Salp15 binding to CD4 is persistent and induces a long-lasting immunomodulatory effect. The activity of Salp15 results in sustained diminished cross-antigenic antibody production even after interruption of the treatment with the protein...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28873074/adipose-derived-cellular-therapies-in-solid-organ-and-vascularized-composite-allotransplantation
#9
Katlin B Stivers, Jason E Beare, Paula M Chilton, Stuart K Williams, Christina L Kaufman, James B Hoying
PURPOSE OF REVIEW: Controlling acute allograft rejection following vascularized composite allotransplantation requires strict adherence to courses of systemic immunosuppression. Discovering new methods to modulate the alloreactive immune response is essential for widespread application of vascularized composite allotransplantation. Here, we discuss how adipose-derived cellular therapies represent novel treatment options for immune modulation and tolerance induction in vascularized composite allotransplantation...
October 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28855905/mesenchymal-stem-cells-may-ameliorate-nephrotic-syndrome-post-allogeneic-hematopoietic-stem-cell-transplantation-case-report
#10
Xin Zhang, Yanwen Peng, Zhiping Fan, Ke Zhao, Xiaoyong Chen, Ren Lin, Jing Sun, Guobao Wang, AndyPeng Xiang, Qifa Liu
INTRODUCTION: Because of their immunomodulatory and anti-inflammatory effects, mesenchymal stem cells (MSCs) have been considered as potential therapeutic agents for treating immune-related or autoimmune diseases, such as graft-versus-host disease (GVHD). Nephrotic syndrome (NS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an uncommon complication with unclear etiology and pathogenesis. It may be an immune disorder involving immune complex deposition, B cells, regulatory T cells (Tregs), and Th1 cytokines and be a manifestation of chronic GVHD...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28842469/a20-restrains-thymic-regulatory-t-cell-development
#11
Julius Clemens Fischer, Vera Otten, Maike Kober, Christoph Drees, Marc Rosenbaum, Martina Schmickl, Simon Heidegger, Rudi Beyaert, Geert van Loo, Xian Chang Li, Christian Peschel, Marc Schmidt-Supprian, Tobias Haas, Silvia Spoerl, Hendrik Poeck
Maintaining immune tolerance requires the production of Foxp3-expressing regulatory T (Treg) cells in the thymus. Activation of NF-κB transcription factors is critically required for Treg cell development, partly via initiating Foxp3 expression. NF-κB activation is controlled by a negative feedback regulation through the ubiquitin editing enzyme A20, which reduces proinflammatory signaling in myeloid cells and B cells. In naive CD4(+) T cells, A20 prevents kinase RIPK3-dependent necroptosis. Using mice deficient for A20 in T lineage cells, we show that thymic and peripheral Treg cell compartments are quantitatively enlarged because of a cell-intrinsic developmental advantage of A20-deficient thymic Treg differentiation...
August 25, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28829428/in-vitro-and-in-vivo-assessment-of-t-b-and-myeloid-cells-suppressive-activity-and-humoral-responses-from-transplant-recipients
#12
Séverine Bézie, Claire Usal, Carole Guillonneau
The main concern in transplantation is to achieve specific tolerance through induction of regulatory cells. The understanding of tolerance mechanisms requires reliable models. Here, we describe models of tolerance to cardiac allograft in rat, induced by blockade of costimulation signals or by upregulation of immunoregulatory molecules through gene transfer. Each of these models allowed in vivo generation of regulatory cells such as regulatory T cells (Tregs), regulatory B cells (Bregs) or regulatory myeloid cells (RegMCs)...
August 12, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28807569/il-10-engineered-human-cd4-tr1-cells-eliminate-myeloid-leukemia-in-an-hla-class-i-dependent-mechanism
#13
Grazia Locafaro, Grazia Andolfi, Fabio Russo, Luca Cesana, Antonello Spinelli, Barbara Camisa, Fabio Ciceri, Angelo Lombardo, Attilio Bondanza, Maria Grazia Roncarolo, Silvia Gregori
T regulatory cells (Tregs) play a key role in modulating T cell responses. Clinical trials showed that Tregs modulate graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, their ability to mediate anti-leukemic activity (graft-versus-leukemia [GvL]) is largely unknown. Enforced interleukin-10 (IL-10) expression converts human CD4(+) T cells into T regulatory type 1 (Tr1)-like (CD4(IL-10)) cells that suppress effector T cells in vitro and xenoGvHD in humanized mouse models...
July 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28738016/eomesodermin-promotes-the-development-of-type-1-regulatory-t-tr1-cells
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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