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https://www.readbyqxmd.com/read/29340116/t-follicular-helper-cells-a-potential-therapeutic-target-in-follicular-lymphoma
#1
REVIEW
Jordi Ochando, Mounia S Braza
Follicular lymphoma (FL), the most common indolent B-cell non-Hodgkin lymphoma (B-NHL), is a germinal center (GC)-derived lymphoma. The mechanisms underlying B-cell differentiation/maturation in GCs could be also involved in their malignant transformation. Moreover, the non-malignant cell composition and architecture of the tumor microenvironment can influence FL development and outcome. Here, we review recent research advances on CD4 helper T cells in FL that highlight the pivotal role of T follicular helper (TFH) cells in a complex multicellular system where they interact with B cells during GC dynamics...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29331804/toll-like-receptor-9-antagonist-suppresses-humoral-immunity-in-experimental-autoimmune-myasthenia-gravis
#2
Peng Zhang, Chun-Lin Yang, Ru-Tao Liu, Heng Li, Min Zhang, Na Zhang, Long-Tao Yue, Cong-Cong Wang, Ying-Chun Dou, Rui-Sheng Duan
Recent studies have demonstrated the important role of toll-like receptor 9 (TLR9) signalling in autoimmune diseases, but its role in myasthenia gravis (MG) has not been fully established. We show herein that blocking TLR9 signalling via the suppressive oligodeoxynucleotide (ODN) H154 alleviated the symptoms of experimental autoimmune myasthenia gravis (EAMG). With the downregulation of dendritic cells (DCs), TLR9 interruption reduced follicular helper T cells (Tfh) and germinal centre (GC) B cells, leading to decreased antibody production...
January 11, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29321276/ifn-regulatory-factor-3-balances-th1-and-t-follicular-helper-immunity-during-nonlethal-blood-stage-plasmodium-infection
#3
Kylie R James, Megan S F Soon, Ismail Sebina, Daniel Fernandez-Ruiz, Gayle Davey, Urijah N Liligeto, Arya Sheela Nair, Lily G Fogg, Chelsea L Edwards, Shannon E Best, Lianne I M Lansink, Kate Schroder, Jane A C Wilson, Rebecca Austin, Andreas Suhrbier, Steven W Lane, Geoffrey R Hill, Christian R Engwerda, William R Heath, Ashraful Haque
Differentiation of CD4+ Th cells is critical for immunity to malaria. Several innate immune signaling pathways have been implicated in the detection of blood-stage Plasmodium parasites, yet their influence over Th cell immunity remains unclear. In this study, we used Plasmodium-reactive TCR transgenic CD4+ T cells, termed PbTII cells, during nonlethal P. chabaudi chabaudi AS and P. yoelii 17XNL infection in mice, to examine Th cell development in vivo. We found no role for caspase1/11, stimulator of IFN genes, or mitochondrial antiviral-signaling protein, and only modest roles for MyD88 and TRIF-dependent signaling in controlling PbTII cell expansion...
January 10, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29321143/control-of-humoral-response-in-renal-transplantation-by-belatacept-depends-on-a-direct-effect-on-b-cells-and-impaired-t-follicular-helper-b-cell-crosstalk
#4
Claire Leibler, Allan Thiolat, Carole Hénique, Chloé Samson, Caroline Pilon, Marie Tamagne, France Pirenne, Benoit Vingert, José L Cohen, Philippe Grimbert
Generation of de novo donor-specific antibodies (dnDSAs) after renal transplant is recognized as the leading cause of late transplant failure. Hence, the optimal immunosuppressive strategies to limit dnDSA development need to be defined. Recent clinical trials using the novel costimulatory blockade agent CTLA4-Ig (Belatacept) have shown that kidney transplant recipients (KTRs) treated with Belatacept have better graft survival and function and a lower proportion of dnDSAs than control-treated KTRs. Mechanisms involved in the control of humoral responses by Belatacept remain to be investigated...
January 10, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29315807/karma-or-immortality-can-religion-influence-space-time-mappings
#5
Heng Li, Yu Cao
People implicitly associate the "past" and "future" with "front" and "back" in their minds according to their cultural attitudes toward time. As the temporal focus hypothesis (TFH) proposes, future-oriented people tend to think about time according to the future-in-front mapping, whereas past-oriented people tend to think about time according to the past-in-front mapping (de la Fuente, Santiago, Román, Dumitrache, & Casasanto, 2014). Whereas previous studies have demonstrated that culture exerts an important influence on people's implicit spatializations of time, we focus specifically on religion, a prominent layer of culture, as potential additional influence on space-time mappings...
January 9, 2018: Cognitive Science
https://www.readbyqxmd.com/read/29297233/deficiency-of-autoimmune-regulator-impairs-the-immune-tolerance-effect-of-bone-marrow-derived-dendritic-cells-in-mice
#6
Feifei Huo, Dongbei Li, Bo Zhao, Yadong Luo, Bingjie Zhao, Xueyang Zou, Yi Li, Wei Yang
As a transcription factor, autoimmune regulator (Aire) participates in thymic negative selection and maintains immune tolerance mainly by regulating the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs). Aire is also expressed in dendritic cells (DCs). DCs are professional antigen-presenting cells (APCs) that affect the differentiation of T cells toward distinct subpopulations and participate in the immune response and tolerance, thereby playing an important role in maintaining homeostasis...
January 3, 2018: Autoimmunity
https://www.readbyqxmd.com/read/29296858/successful-desensitization-with-proteasome-inhibition-and-costimulation-blockade-in-sensitized-nonhuman-primates
#7
Jean Kwun, Christopher Burghuber, Miriam Manook, Brian Ezekian, Jaeberm Park, Janghoon Yoon, John S Yi, Neal Iwakoshi, Adriana Gibby, Jung Joo Hong, Alton B Farris, Allan D Kirk, Stuart J Knechtle
The detrimental effects of donor-directed antibodies in sensitized transplant patients remain a difficult immunologic barrier to successful organ transplantation. Antibody removal is often followed by rebound. Proteasome inhibitors (PIs) deplete antibody-producing plasma cells (PCs) but have shown marginal benefit for desensitization. In an allosensitized nonhuman primate (NHP) model, we observed increased germinal center (GC) formation after PI monotherapy, suggesting a compensatory PC repopulation mediated via GC activation...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29288900/increased-pd-1-cd154-tfh-cells-are-possibly-the-most-important-functional-subset-of-pd-1-t-follicular-helper-cells-in-adult-patients-with-minimal-change-disease
#8
Tao Li, Yunpeng Shi, Weixia Sun, Haifeng Wang, Quan Wang, Yanfang Jiang
T follicular helper (Tfh) cells, especially programmed cell death protein 1 (PD-1)+ Tfh cells, exert important functions in the normal immune response. The purpose of this study was to determine the frequency of different subsets of PD-1+ Tfh cells and their functional effects in adult patients with minimal change disease (MCD). The frequencies of circulating PD-1+, PD-1+CD154+, and PD-1+interleukin (IL)-21+ Tfh cells, and CD38+CD19+ and CD38+CD19+CD40+ B cells, as well as serum IL-2, IL-4, IL-17A, IL-6, IL-21, and interferon (IFN)-γ were significantly increased in the MCD patients compared with the healthy controls (HCs) (P < 0...
December 27, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29288344/fdc-tfh-interactions-within-cervical-lymph-nodes-of-siv-infected-rhesus-macaques
#9
Rajnish S Dave, Ravi K Sharma, Roshell R Muir, Elias Haddad, Sanjeev Gumber, Francois Villinger, Artinder P Nehra, Zafar K Khan, Brian Wigdahl, Aftab A Ansari, Siddappa N Byrareddy, Pooja Jain
Cerebrospinal fluid (CSF) drains via the lymphatic drainage pathway. This lymphatic pathway connects the central nervous system (CNS) to the cervical lymph node (CLN). As the CSF drains to CLN via the dural and nasal lymphatics, T cells and antigen presenting cells pass along the channels from the subarachnoid space through the cribriform plate. Human immunodeficiency virus (HIV) may also egress from the CNS along this pathway. As a result, HIV egressing from the CNS may accumulate within the CLN. Towards this objective, we analyzed CLNs isolated from rhesus macaques that were chronically-infected with simian immunodeficiency virus (SIV)...
December 29, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/29283192/functional-and-phenotypical-analysis-of-il-6-secreting-cd4-t-cells-in-human-adipose-tissue
#10
Anja J de Jong, Sabrina Pollastro, Joanneke C Kwekkeboom, Stefan N Andersen, Annemarie L Dorjée, Aleida M Bakker, Fawaz Alzaid, Antoine Soprani, Rob G H H Nelissen, Jan B Mullers, Nicolas Venteclef, Niek de Vries, Margreet Kloppenburg, René E M Toes, Andreea Ioan-Facsinay
Emerging evidence indicates that a dynamic interplay between the immune system and adipocytes contributes to the disturbed homeostasis in adipose tissue of obese subjects. Recently, we observed IL-6-secretion by CD4+ T cells from the stromal vascular fraction (SVF) of the infrapatellar fat pad (IFP) of knee osteoarthritis patients directly ex vivo. Here we show that human IL-6+ CD4+ T cells from SVF display a more activated phenotype than the IL-6- T cells, as evidenced by the expression of the activation marker CD69...
December 28, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29279549/recent-progress-in-the-understanding-of-angioimmunoblastic-t-cell-lymphoma
#11
Manabu Fujisawa, Shigeru Chiba, Mamiko Sakata-Yanagimoto
Angioimmunoblastic T-cell lymphoma (AITL) has been classified as a subtype of mature T-cell neoplasms. The recent revision of the WHO classification proposed a new category of nodal T-cell lymphoma with follicular helper T (TFH)-cell phenotype, which was classified into three diseases: AITL, follicular T-cell lymphoma, and nodal peripheral T-cell lymphoma with TFH phenotype. These lymphomas are defined by the expression of TFH-related antigens, CD279/PD-1, CD10, BCL6, CXCL13, ICOS, SAP, and CXCR5. Although recurrent mutations in TET2, IDH2, DNMT3A, RHOA, and CD28, as well as gene fusions, such as ITK-SYK and CTLA4-CD28, were not diagnostic criteria, they may be considered as novel criteria in the near future...
2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/29249358/initiation-of-antiviral-b-cell-immunity-relies-on-innate-signals-from-spatially-positioned-nkt-cells
#12
Mauro Gaya, Patricia Barral, Marianne Burbage, Shweta Aggarwal, Beatriz Montaner, Andrew Warren Navia, Malika Aid, Carlson Tsui, Paula Maldonado, Usha Nair, Khader Ghneim, Padraic G Fallon, Rafick-Pierre Sekaly, Dan H Barouch, Alex K Shalek, Andreas Bruckbauer, Jessica Strid, Facundo D Batista
B cells constitute an essential line of defense from pathogenic infections through the generation of class-switched antibody-secreting cells (ASCs) in germinal centers. Although this process is known to be regulated by follicular helper T (TfH) cells, the mechanism by which B cells initially seed germinal center reactions remains elusive. We found that NKT cells, a population of innate-like T lymphocytes, are critical for the induction of B cell immunity upon viral infection. The positioning of NKT cells at the interfollicular areas of lymph nodes facilitates both their direct priming by resident macrophages and the localized delivery of innate signals to antigen-experienced B cells...
December 12, 2017: Cell
https://www.readbyqxmd.com/read/29247716/airway-exposure-initiates-peanut-allergy-by-involving-the-il-1-pathway-and-t-follicular-helper-cells-in-mice
#13
Joseph J Dolence, Takao Kobayashi, Koji Iijima, James Krempski, Li Y Drake, Alexander L Dent, Hirohito Kita
BACKGROUND: Little is currently known regarding the immunological mechanism(s) that initiate peanut allergy. Notably, peanut proteins have been detected in house dust, and their levels correlate with peanut allergy prevalence. OBJECTIVE: This study aimed to develop a new mouse model for peanut allergy and to investigate the immunological mechanisms involved in peanut allergen sensitization. METHODS: To mimic environmental exposure, naïve mice were exposed to peanut flour by inhalation for up to 4 weeks...
December 13, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29247364/laparoscopic-repair-of-traumatic-flank-hernias
#14
Y W Novitsky
INTRODUCTION: Traumatic flank hernias (TFH) are caused by a blunt abdominal trauma with resultant detachment of the oblique musculofascial complex at the iliac crest and/or costal margin. Given such proximity to the bony structures and essential absence of healthy fascia to anchor the mesh, TFH represent a challenging surgical problem. Although laparoscopic repair of ventral hernias has become very common, no series of laparoscopic repairs of TFH has been reported to date. We present a series of patients undergoing laparoscopic repair of TFH...
December 15, 2017: Hernia: the Journal of Hernias and Abdominal Wall Surgery
https://www.readbyqxmd.com/read/29246441/roquin-suppresses-the-pi3k-mtor-signaling-pathway-to-inhibit-t-helper-cell-differentiation-and-conversion-of-treg-to-tfr-cells
#15
Katharina Essig, Desheng Hu, Joao C Guimaraes, Dominik Alterauge, Stephanie Edelmann, Timsse Raj, Jan Kranich, Gesine Behrens, Alexander Heiseke, Stefan Floess, Juliane Klein, Andreas Maiser, Susan Marschall, Martin Hrabĕ de Angelis, Heinrich Leonhardt, Cornelis F Calkhoven, Elfriede Noessner, Thomas Brocker, Jochen Huehn, Anne B Krug, Mihaela Zavolan, Dirk Baumjohann, Vigo Heissmeyer
Roquin proteins preclude spontaneous T cell activation and aberrant differentiation of T follicular helper (Tfh) or T helper 17 (Th17) cells. Here we showed that deletion of Roquin-encoding alleles specifically in regulatory T (Treg) cells also caused the activation of conventional T cells. Roquin-deficient Treg cells downregulated CD25, acquired a follicular Treg (Tfr) cell phenotype, and suppressed germinal center reactions but could not protect from colitis. Roquin inhibited the PI3K-mTOR signaling pathway by upregulation of Pten through interfering with miR-17∼92 binding to an overlapping cis-element in the Pten 3' UTR, and downregulated the Foxo1-specific E3 ubiquitin ligase Itch...
December 12, 2017: Immunity
https://www.readbyqxmd.com/read/29242501/high-throughput-rna-sequencing-reveals-distinct-gene-signatures-in-active-igg4-related-disease
#16
Brandon W Higgs, Yanying Liu, Jianping Guo, Yinong Sebastian, Chris Morehouse, Wei Zhu, Limin Ren, Mengru Liu, Yan Du, Guangyan Yu, Lingli Dong, Hong Hua, Pan Wei, Yi Wang, Zhengang Wang, Yihong Yao, Zhan-Guo Li
We aimed to characterize the molecular differences and effects from prednisone treatment among IgG4-related disease with salivary gland lesions (RD-SG), without SG lesions (RD-nonSG), and IgG4-related retroperitoneal fibrosis (RF). RNA sequencing was conducted on blood from 25 RD-SG, 11 RD-nonSG, 3 RF and 10 control subjects. Among these, 8 RD-nonSG and 12 RD-SG patients were subjected to treatment with prednisone and/or glucocorticoid-sparing agents. Six RD patients had a longitudinal time point. The mRNA levels of IgG4 and IgE, genes specific for Th2 cells, eosinophils, and neutrophils were over-expressed in RD-SG and RD-nonSG...
December 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29241019/quantitative-analysis-of-a-multiplexed-immunofluorescence-panel-in-t-cell-lymphoma
#17
Siok-Bian Ng, Shuangyi Fan, Shoa-Nian Choo, Michal Hoppe, Hoang Mai Phuong, Sanjay De Mel, Anand D Jeyasekharan
Immunohistochemistry (IHC) provides clinically useful information on protein expression in cancer cells. However, quantification of colocalizing signals using conventional IHC and visual scores is challenging. Here we describe the application of quantitative immunofluorescence in angioimmunoblastic T-cell lymphoma (AITL), a peripheral T-cell lymphoma characterized by cellular heterogeneity that impedes IHC interpretation and quantification. A multiplexed immunofluorescence (IF) panel comprising T- and B-lymphocyte markers along with T-follicular helper (TFH) markers was validated for appropriate cellular localization in sections of benign tonsillar tissue and tested in two samples of AITL, using a Vectra microscope for spectral imaging and InForm software for analysis...
December 1, 2017: SLAS Technology
https://www.readbyqxmd.com/read/29236760/distribution-of-circulating-t-follicular-helper-cell-subsets-is-altered-in-immunoglobulin-a-vasculitis-in-children
#18
Deying Liu, Jinxiang Liu, Jinghua Wang, Lishuang Guo, Congcong Liu, Yanfang Jiang, Haifeng Wang, Sirui Yang
BACKGROUND: Immunoglobulin A vasculitis (IgAV) is the most common vasculitis in children. Previously, we demonstrated that patients with IgAV show abnormal proliferation of cluster of differentiation (CD)4+C-X-C chemokine receptor type (CXCR)5+ follicular helper T (Tfh) cells. Here, we explored the status of Tfh cell subsets and plasma cytokine levels in patients with IgAV. METHODS: CD4+CXCR5+CD45RA-, CD45RA-CXCR3+CCR6-, CD45RA-CXCR3-CCR6-, CD45RA-CXCR3-CCR6+, and CD45RA-CXCR3+CCR6+ Tfh cell fractions and plasma concentrations of interferon-γ, interleukin (IL)-4, and IL-17A were evaluated by flow cytometry and a flow cytometric bead array, respectively, in 30 patients with IgAV and 15 healthy controls (HCs)...
2017: PloS One
https://www.readbyqxmd.com/read/29228688/altered-follicular-helper-t-cell-impaired-antibody-production-in-a-murine-model-of-myelodysplastic-syndromes
#19
Huijuan Jiang, Ningbo Cui, Liyan Yang, Chunyan Liu, Lanzhu Yue, Lifang Guo, Huaquan Wang, Zonghong Shao
Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic diseases which have a high risk of progressing to acute myeloid leukemia. MDS patients have immunologic deficiency, including T and B cells dysfunction. Follicular T helper cells (Tfh, CD4+CXCR5+) are an important subset of helper T cells which help to the formation of germinal centers and B cells differentiation. In this study, we investigated the proportion and function of Tfh using NUP98-HOXD13 transgenic (NHD13) mice model with MDS phenotype...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29223395/a-novel-mouse-model-for-tracking-the-fate-of-cxcr5-expressing-t-cells
#20
Tomo Takebe, Kazuki Sakamoto, Yoshikazu Higami, Yohsuke Harada
The germinal center (GC) reaction, a critical process in the humoral immune response, requires follicular helper T (Tfh) cells. Tfh cells express the master transcription factor Bcl6 and chemokine receptor CXCR5, which enable them to migrate from the T cell zone to B cell follicles and interact with GC B cells. However, CXCR5 is downregulated when Tfh cells become memory cells. Therefore, it is difficult to track Tfh cells continuously in vivo. In this study, we generated a mouse strain, Cxcr5CreERT2R26Tomato, in which the fluorescent protein tdTomato is inducibly expressed in CXCR5+ cells by tamoxifen administration...
January 8, 2018: Biochemical and Biophysical Research Communications
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