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Regulatory B cell in transplantation

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https://www.readbyqxmd.com/read/27902485/impacts-of-cigarette-smoking-on-immune-responsiveness-up-and-down-or-upside-down
#1
REVIEW
Feifei Qiu, Chun-Ling Liang, Huazhen Liu, Yu-Qun Zeng, Shaozhen Hou, Song Huang, Xiaoping Lai, Zhenhua Dai
Cigarette smoking is associated with numerous diseases and poses a serious challenge to the current healthcare system worldwide. Smoking impacts both innate and adaptive immunity and plays dual roles in regulating immunity by either exacerbation of pathogenic immune responses or attenuation of defensive immunity. Adaptive immune cells affected by smoking mainly include T helper cells (Th1/Th2/Th17), CD4+CD25+ regulatory T cells, CD8+ T cells, B cells and memory T/B lymphocytes while innate immune cells impacted by smoking are mostly DCs, macrophages and NK cells...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900346/preclinical-development-and-qualification-of-zfn-mediated-ccr5-disruption-in-human-hematopoietic-stem-progenitor-cells
#2
David L DiGiusto, Paula M Cannon, Michael C Holmes, Lijing Li, Anitha Rao, Jianbin Wang, Gary Lee, Philip D Gregory, Kenneth A Kim, Samuel B Hayward, Kathleen Meyer, Colin Exline, Evan Lopez, Jill Henley, Nancy Gonzalez, Victoria Bedell, Rodica Stan, John A Zaia
Gene therapy for HIV-1 infection is a promising alternative to lifelong combination antiviral drug treatment. Chemokine receptor 5 (CCR5) is the coreceptor required for R5-tropic HIV-1 infection of human cells. Deletion of CCR5 renders cells resistant to R5-tropic HIV-1 infection, and the potential for cure has been shown through allogeneic stem cell transplantation with naturally occurring homozygous deletion of CCR5 in donor hematopoietic stem/progenitor cells (HSPC). The requirement for HLA-matched HSPC bearing homozygous CCR5 deletions prohibits widespread application of this approach...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27888331/the-origin-of-dcs-and-capacity-for-immunologic-tolerance-in-central-and-peripheral-tissues
#3
REVIEW
K Sanjana P Devi, Niroshana Anandasabapathy
Dendritic cells (DCs) are specialized immune sentinels that play key role in maintaining immune homeostasis by efficiently regulating the delicate balance between protective immunity and tolerance to self. Although DCs respond to maturation signals present in the surrounding milieu, multiple layers of suppression also co-exist that reduce the infringement of tolerance against self-antigens. These tolerance inducing properties of DCs are governed by their origin and a range of other factors including distribution, cytokines, growth factors, and transcriptional programing, that collectively impart suppressive functions to these cells...
November 25, 2016: Seminars in Immunopathology
https://www.readbyqxmd.com/read/27863545/porcine-treg-depletion-with-a-novel-diphtheria-toxin-based-anti-human-ccr4-immunotoxin
#4
Zhaohui Wang, Nalu Navarro-Alvarez, Jigesh A Shah, Huiping Zhang, Qi Huang, Qian Zheng, Joren C Madsen, David H Sachs, Christene A Huang, Zhirui Wang
Regulatory T cells (Tregs) are known to play an important role in immunoregulation and have been shown to facilitate induction of transplantation tolerance. Chemokine (C-C motif) receptor 4 (CCR4) is expressed on the surface of effector Tregs involved in controlling alloimmune and autoimmune responses. Recently we have developed a novel diphtheria-toxin based anti-human CCR4 immunotoxin for depleting CCR4(+) cells in vivo. In this study, we have demonstrated that the anti-human CCR4 immunotoxin bound to porcine lymphocytes including CD4(+)FoxP3(+) Tregs...
December 2016: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/27853649/cd24-blunts-oral-squamous-cancer-development-and-dampens-the-functional-expansion-of-myeloid-derived-suppressor-cells
#5
Caroline W Fugle, Yongliang Zhang, Feng Hong, Shaoli Sun, Caroline Westwater, Saleh Rachidi, Hong Yu, Elizabeth Garret-Mayer, Keith Kirkwood, Bei Liu, Zihai Li
CD24 expression has been implicated in the oncogenesis of multiple types of cancer and high tumor expression is considered a poor prognosis factor; however, the role of CD24 in oral cancer progression is unknown. Unlike other cancer types, we found that higher CD24 levels in human oral cancers are correlated to lower clinical stage and better overall survival. We then dissected the role of CD24 and mechanisms in oral cancer pathogenesis in mice using a genetic strategy and demonstrated that CD24 deficiency increased the oral cavity tumor burden in response to the carcinogen 4-nitroquioline 1-oxide (4-NQO)...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27821504/chronic-graft-versus-host-disease-biological-insights-from-pre-clinical-and-clinical-studies
#6
Kelli P A MacDonald, Geoffrey R Hill, Bruce R Blazar
With the increasingly use of mismatched, unrelated and G-CSF mobilized peripheral blood stem cell donor grafts and successful treatment of older recipients, chronic graft-versus-host disease (cGVHD) has emerged as the major cause of non-relapse mortality and morbidity. Chronic GVHD is characterized by lichenoid changes and fibrosis that affects a multitude of tissues, compromising organ function. Beyond steroids, effective treatment options are limited. Thus new strategies to both prevent and treat disease are urgently required...
November 7, 2016: Blood
https://www.readbyqxmd.com/read/27805502/cell-therapy-in-solid-organ-transplant
#7
Hassan Argani
In solid-organ transplant, cell therapy is used as an immunomodulation therapy or as a functioning graft (bioengineering medicine). Before such treatment can be more accepted among transplant societies, some uncertainties should be clarified. These include: why is such therapy mandatory? What are the indications for this therapy, and what are the mechanism(s) of actions? What types of cells are involved and what are their routes of actions? Finally, what is known about the safety? In general, the risks associated with intravenous administration of immunoregulatory cell products are similar to those encountered with conventional blood transfusions...
November 2016: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/27798706/application-of-high-throughput-next-generation-sequencing-for-hla-typing-on-buccal-extracted-dna-results-from-over-10-000-donor-recruitment-samples
#8
Yuxin Yin, James H Lan, David Nguyen, Nicole Valenzuela, Ping Takemura, Yung-Tsi Bolon, Brianna Springer, Katsuyuki Saito, Ying Zheng, Tim Hague, Agnes Pasztor, Gyorgy Horvath, Krisztina Rigo, Elaine F Reed, Qiuheng Zhang
BACKGROUND: Unambiguous HLA typing is important in hematopoietic stem cell transplantation (HSCT), HLA disease association studies, and solid organ transplantation. However, current molecular typing methods only interrogate the antigen recognition site (ARS) of HLA genes, resulting in many cis-trans ambiguities that require additional typing methods to resolve. Here we report high-resolution HLA typing of 10,063 National Marrow Donor Program (NMDP) registry donors using long-range PCR by next generation sequencing (NGS) approach on buccal swab DNA...
2016: PloS One
https://www.readbyqxmd.com/read/27797959/hookworm-recombinant-protein-promotes-regulatory-t-cell-responses-that-suppress-experimental-asthma
#9
Severine Navarro, Darren A Pickering, Ivana B Ferreira, Linda Jones, Stephanie Ryan, Sally Troy, Andrew Leech, Peter J Hotez, Bin Zhan, Thewarach Laha, Roger Prentice, Tim Sparwasser, John Croese, Christian R Engwerda, John W Upham, Valerie Julia, Paul R Giacomin, Alex Loukas
In the developed world, declining prevalence of some parasitic infections correlates with increased incidence of allergic and autoimmune disorders. Moreover, experimental human infection with some parasitic worms confers protection against inflammatory diseases in phase 2 clinical trials. Parasitic worms manipulate the immune system by secreting immunoregulatory molecules that offer promise as a novel therapeutic modality for inflammatory diseases. We identify a protein secreted by hookworms, anti-inflammatory protein-2 (AIP-2), that suppressed airway inflammation in a mouse model of asthma, reduced expression of costimulatory markers on human dendritic cells (DCs), and suppressed proliferation ex vivo of T cells from human subjects with house dust mite allergy...
October 26, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27774524/granzyme-b-contributes-to-the-optimal-graft-versus-tumor-effect-mediated-by-conventional-cd4-t-cells
#10
Wei Du, Nicholas D Leigh, Guanglin Bian, Emad Alqassim, Rachel E O'Neill, Lin Mei, Jingxin Qiu, Hong Liu, Philip L McCarthy, Xuefang Cao
Granzyme B (GzmB) is a key cytotoxic molecule utilized by T cells to kill pathogen-infected cells or transformed tumor cells. Previous studies using allogeneic hematopoietic cell transplantation (allo-HCT) murine models showed that GzmB is required for CD8(+) T cells to cause graft-versus-host disease (GVHD). However, our recent study demonstrated that GzmB-mediated damage of CD8(+) T cells diminished their graft-versus-tumor (GVT) activity. In this study, we examined the role of GzmB in GVT effect mediated by conventional CD4(+)CD25(-) T cells (CD4(+) Tcon)...
2016: Journal of Immunology Research and Therapy
https://www.readbyqxmd.com/read/27758892/e2a-pbx1-remodels-oncogenic-signaling-networks-in-b-cell-precursor-acute-lymphoid-leukemia
#11
Jesús Duque-Afonso, Chiou-Hong Lin, Kyuho Han, Michael C Wei, Jue Feng, Jason H Kurzer, Corina Schneidawind, Stephen Hon-Kit Wong, Michael C Bassik, Michael L Cleary
There is limited understanding of how signaling pathways are altered by oncogenic fusion transcription factors that drive leukemogenesis. To address this, we interrogated activated signaling pathways in a comparative analysis of mouse and human leukemias expressing the fusion protein E2A-PBX1, which is present in 5%-7% of pediatric and 50% of pre-B-cell receptor (preBCR(+)) acute lymphocytic leukemia (ALL). In this study, we describe remodeling of signaling networks by E2A-PBX1 in pre-B-ALL, which results in hyperactivation of the key oncogenic effector enzyme PLCγ2...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27740634/which-patients-with-myelofibrosis-should-receive-ruxolitinib-therapy-eln-sie-evidence-based-recommendations
#12
M Marchetti, G Barosi, F Cervantes, G Birgegård, M Griesshammer, C Harrison, R Hehlmann, J-J Kiladjian, N Kröger, M F McMullin, F Passamonti, A Vannucchi, T Barbui
Ruxolitinib is an oral JAK1/JAK2 inhibitor approved for the treatment of patients with myelofibrosis (MF) based on the results of two randomized clinical trials. However, discordant indications were provided by regulatory agencies and scientific societies for selecting the most appropriate candidates to this drug. The European LeukemiaNet and the Italian Society of Hematology shared the aim of building evidence-based recommendations for the use of ruxolitinib according to the GRADE methodology. Eighteen patient-intervention-comparator-outcome profiles were listed, each of them comparing ruxolitinib to other therapies with the aim of improving one of three clinical outcomes: a) splenomegaly, b) disease-related symptoms, and c) survival...
October 14, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27732962/soluble-fibrinogen-like-protein-2-sfgl2-the-novel-effector-molecule-for-immunoregulation
#13
Xin-Guang Liu, Yu Liu, Feng Chen
Soluble fibrinogen-like protein 2 (sFGL2) is the soluble form of fibrinogen-like protein 2 belonging to the fibrinogen-related protein superfamily. It is now well characterized that sFGL2 is mainly secreted by regulatory T cell (Treg) populations, and exerts potently immunosuppressive activities. By repressing not only the differentiation and proliferation of T cells but also the maturation of dendritic cells (DCs), sFGL2 acts largely as an immunosuppressant. Moreover, sFGL2 also induces apoptosis of B cells, tubular epithelial cells (TECs), sinusoidal endothelial cells (SECs), and hepatocytes...
October 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27717015/regulatory-b10-cells-display-an-altered-homeostasis-in-acute-graft-versus-host-disease
#14
Geothy Chakupurakal, María Alejandra Garcia-Marquez, Alexander Shimabukuro-Vornhagen, Sandra Kluth, Hans Schlosser, Sebastian Theurich, Christof Scheid, Michael Hallek, Udo Holtick, Michael von Bergwelt-Baildon
OBJECTIVE: The role of B-cells and the subgroup of IL-10 producing B-cells, known to have a regulatory function, in patients following a haematopoetic stem cell transplant (alloSCT) has not been clearly understood to date. METHODS: We prospectively recruited 95 patients following an alloSCT and studied the B-cell reconstitution on days 30, 90 and 150. Regulatory B10-cells could be analysed in 22 consecutively recruited patients on day 30 post transplant. RESULTS: The total B-cell percentages in transplant recipients (median 0...
September 26, 2016: European Journal of Haematology
https://www.readbyqxmd.com/read/27667759/b10-cells-play-a-role-in-the-immune-modulation-of-pro-and-anti-inflammatory-immune-responses-in-mouse-islet-allograft-rejection
#15
Yao Qin, Mei Zhang, Rui-Mei Jiang, Qian Wu, Xin-Yu Xu, Heng Chen, Tao Yang
Recently, pancreatic islet transplantation has been shown to be a viable option for the treatment of type 1 diabetes mellitus. However, immune destruction becomes the major impediment to the clinical application of islet transplantation. Here, we evaluated changes affecting multiple types of immune cells and cytokines in allogeneic islet transplantation immunity after the administration of B10 cells alone and explored the regulatory mechanisms of B10 cells in T cell-mediated allograft rejection. In vitro assays, B10 cells significantly decreased the proliferative capacity of CD4(+)CD25(-) T cells (13...
September 19, 2016: Cellular Immunology
https://www.readbyqxmd.com/read/27636772/current-status-of-tolerance-in-kidney-transplantation
#16
Sindhu Chandran, Sandy Feng
PURPOSE OF REVIEW: The attainment of tolerance remains a highly desirable goal in recipients of kidney transplants. Achievement of this goal would extend graft survival and eradicate toxicities related to long-term immunosuppression. Understanding mechanisms of tolerance and strategies to induce tolerance - their risk/benefit profiles - is essential for future success. RECENT FINDINGS: Mechanistic studies of spontaneously tolerant kidney transplant recipients have uncovered potential roles for B or regulatory T cells, or both, in the maintenance of tolerance...
November 2016: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/27587399/epithelial-expression-of-human-abo-blood-group-genes-is-dependent-upon-a-downstream-regulatory-element-functioning-through-an-epithelial-cell-specific-transcription-factor-elf5
#17
Rie Sano, Tamiko Nakajima, Yoichiro Takahashi, Rieko Kubo, Momoko Kobayashi, Keiko Takahashi, Haruo Takeshita, Kenichi Ogasawara, Yoshihiko Kominato
The human ABO blood group system is of great importance in blood transfusion and organ transplantation. The ABO system is composed of complex carbohydrate structures that are biosynthesized by A- and B-transferases encoded by the ABO gene. However, the mechanisms regulating ABO gene expression in epithelial cells remain obscure. On the basis of DNase I-hypersensitive sites in and around ABO in epithelial cells, we prepared reporter plasmid constructs including these sites. Subsequent luciferase assays and histone modifications indicated a novel positive regulatory element, designated the +22...
October 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27586805/resetting-the-immune-system-with-immunoablation-and-autologous-haematopoietic-stem-cell-transplantation-in-autoimmune-diseases
#18
REVIEW
Tobias Alexander, Renate Arnold, Falk Hiepe, Andreas Radbruch
Over the past 20 years, immunoablation followed by transplantation of autologous haematopoietic stem cells (ASCT) has emerged as a promising treatment option for patients with severe forms of autoimmune diseases (ADs) that insufficiently respond to standard immunosuppressive or novel biologic treatment. Meanwhile, mechanistic studies have provided the proof-of-concept that the long-term, treatment-free remissions achieved by ASCT are associated with the eradication of the autoreactive immunologic memory and a fundamental reconfiguration of the immune system...
July 2016: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/27574642/role-of-cd8-regulatory-t-cells-in-organ-transplantation
#19
Jiyan Su, Qingfeng Xie, Yang Xu, Xian C Li, Zhenhua Dai
CD8(+) T cells are regulatory T cells (Tregs) that suppress both alloimmunity and autoimmunity in many animal models. This class of regulatory cells includes the CD8(+)CD28(-), CD8(+)CD103(+), CD8(+)FoxP3(+) and CD8(+)CD122(+) subsets. The mechanisms of action of these regulatory cells are not fully understood; however, the secretion of immunosuppressive cytokines, such as interleukin (IL)-4, IL-10 and transforming growth factor beta (TGF-β) as well as the direct killing of target cells via Fas L/Fas and the perforin/granzyme B pathways have been demonstrated in various models...
2014: Burns and trauma
https://www.readbyqxmd.com/read/27546296/aged-b-cells-alter-immune-regulation-of-allografts-in-mice
#20
Daniel N Mori, Hua Shen, Anjela Galan, Daniel R Goldstein
Organ transplantation in older people is increasing, but how aging impacts B-cell responses to organ transplantation is still unknown. Here, we show that the depletion of B-cells with anti-CD20 antibodies has disparate effects depending on recipient age. In young murine recipients, anti-CD20 treatment impaired the ability of immune modulation to extend skin allograft survival. In contrast, anti-CD20 treatment extended allograft survival in aged recipients treated with immune modulation. Although regulatory B-cell function and the numbers of marginal and follicular B cells were similar between age groups, a subpopulation of B cells, termed age-associated B cells (ABCs), accumulated upon aging...
August 22, 2016: European Journal of Immunology
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