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https://www.readbyqxmd.com/read/28428235/anti-cd20-il-21-fusokine-the-tail-wags-the-dog
#1
Stephen M Ansell
No abstract text is available yet for this article.
April 20, 2017: Blood
https://www.readbyqxmd.com/read/28428203/tslp-activated-dendritic-cells-induce-human-t-follicular-helper-cell-differentiation-through-ox40-ligand
#2
Lucia Pattarini, Coline Trichot, Sofia Bogiatzi, Maximilien Grandclaudon, Stephan Meller, Zela Keuylian, Melanie Durand, Elisabetta Volpe, Stefania Madonna, Andrea Cavani, Andrea Chiricozzi, Marco Romanelli, Toshiyuki Hori, Alain Hovnanian, Bernhard Homey, Vassili Soumelis
T follicular helper cells (Tfh) are important regulators of humoral responses. Human Tfh polarization pathways have been thus far associated with Th1 and Th17 polarization pathways. How human Tfh cells differentiate in Th2-skewed environments is unknown. We show that thymic stromal lymphopoietin (TSLP)-activated dendritic cells (DCs) promote human Tfh differentiation from naive CD4 T cells. We identified a novel population, distinct from Th2 cells, expressing IL-21 and TNF, suggestive of inflammatory cells...
April 20, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28427414/observational-study-of-interleukin-21-il-21-does-not-distinguish-kawasaki-disease-from-other-causes-of-fever-in-children
#3
Rachel Engelberg, Meghan Martin, Brian H Wrotniak, Mark Daniel Hicar
BACKGROUND: Kawasaki disease (KD) is a febrile childhood vasculitis of unknown etiology. The diagnosis is highly concerning as over a quarter of children who fail to receive timely treatment with intravenous immunoglobulin (IVIG) will develop coronary aneurysms. Diagnosis relies on proper symptomatology and is supported by non-specific markers of inflammation. Previous studies have identified elevated plasma levels of interleukin-21 (IL-21) as a sensitive and specific biomarker in KD...
April 20, 2017: Pediatric Rheumatology Online Journal
https://www.readbyqxmd.com/read/28413901/elevation-of-cd16-cd56-nk-cells-and-down-regulation-of-serum-interleukin-21-il-21-and-il-1%C3%AE-after-splenectomy-in-relapsed-hemophagocytic-lymphohistiocytosis-of-unknown-cause
#4
Jingshi Wang, Wei Han, Zhuo Gao, Yini Wang, Lin Wu, Jia Zhang, Wenyuan Lai, Zhao Wang
OBJECTIVES: Encouraging progress has been made in application of splenectomy in the treatment of relapsed hemophagocytic lymphohistiocytosis (HLH) of unknown cause. The aim was to determine the roles of lymphocyte subpopulations and inflammatory cytokines in splenectomy. METHODS: We retrospectively analyzed changes in lymphocyte subpopulations and levels of inflammatory cytokines at different time-points before and after splenectomy in the patients with relapsed HLH of unknown cause, as well as the correlations between these changes and the disease prognosis...
April 15, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28408722/ephrin-b1-mediated-repulsion-and-signaling-control-germinal-center-t-cell-territoriality-and-function
#5
Peiwen Lu, Changming Shih, Hai Qi
Follicular T-helper (TFH) cells orchestrate the germinal center (GC) reaction locally. Local mechanisms regulating their dynamics and helper functions are not well defined. Here we found that GC-expressed Ephrin B1 (EFNB1) repulsively inhibited T cell to B cell adhesion and GC TFH retention by signaling through TFH-expressed EPHB6 receptor. At the same time, EFNB1 promoted IL-21 production from GC TFH cells by signaling predominantly through EPHB4. Consequently, EFNB1-null GCs were associated with defective production of plasma cells despite harboring excessive TFH cells...
April 13, 2017: Science
https://www.readbyqxmd.com/read/28405614/il-21-is-required-for-cd4-memory-formation-in-response-to-viral-infection
#6
Yuqing Yuan, Yiping Yang, Xiaopei Huang
IL-21 has been shown to play an important role in the CD8 T cell response during acute and chronic viral infections. However, the role of IL-21 signaling in the CD4 T cell response to viral infection remains incompletely defined. In a model of infection with vaccinia virus, we show that intrinsic IL-21 signaling on CD4 T cells was critical for the formation of memory CD4 T cells in vivo. We further reveal that IL-21 promoted CD4 T cell survival in a mechanism dependent on activation of the STAT1 and STAT3 signaling pathways...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28397078/elevated-levels-of-tl1a-are-associated-with-disease-activity-in-patients-with-systemic-sclerosis
#7
Wangdong Xu, Linchong Su, Pingying Qing, Ying Wang, Yan Liang, Yi Zhao, Qiongxiu Zhou, Feng Ma, Yi Liu
TL1A is a member of the TNF superfamily. It performs significantly in the pathogenesis of rheumatic and autoimmune diseases partly through regulating the Th17 pathway. The clinical implication of circulating TL1A in patients with systemic sclerosis (SSc) remains unclear, and correlation between TL1A and Th17-related cytokines in the pathogenesis of SSc needs to be discussed. We measured serum levels of TL1A and Th17-related cytokines by ELISA in 47 patients with SSc, 56 patients with SLE, and 53 healthy subjects, and investigated association of these cytokines with clinical manifestations and laboratory variables...
April 10, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28393233/assessment-of-th17-lymphocytes-and-cytokine-il%C3%A2-17a-in-epithelial-ovarian-tumors
#8
Izabela Winkler, Maria Pyszniak, Katarzyna Pogoda, Andrzej Semczuk, Marek Gogacz, Paweł Miotla, Aneta Adamiak, Dorota Darmochwal-Kolarz, Tomasz Rechberger, Jacek Tabarkiewicz
The present study was carried out to assess the percentage of T helper 17 (Th17) lymphocytes in blood and tissue and IL-17A serum concentrations in patients with epithelial ovarian tumors. Two isoforms, IL-17A and IL-17F, as well as IL-21 and IL-22, were simultaneously investigated. The study group consisted of 60 women affected by epithelial ovarian tumors (benign, borderline and malignant) and 20 women without ovarian pathology as a control group. The evaluation of the percentage of Th17 cells secreting IL-17A, IL-17F, IL-21 and IL-22 in peripheral blood and tumor tissues was performed using flow cytometry applying a Th17 cytokine staining panel...
April 6, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28378248/role-of-il-21-in-htlv-1-infections-with-emphasis-on-htlv-1-associated-myelopathy-tropical-spastic-paraparesis-ham-tsp
#9
Taraneh Rajaei, Hamid Farajifard, Houshang Rafatpanah, Reza Bustani, Narges Valizadeh, Bahareh Rajaei, Seyed Abdolrahim Rezaee
Interleukin-21 (IL-21) enhances the survival and cytotoxic properties of cytotoxic T cells (CTLs) and exhibits essential roles in controlling chronic viral infections. HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive inflammatory disease of the nervous system. The main determinant of disease progression is efficiency of the CTL response to Human T lymphotropic virus types I (HTLV-1). In this study, the expression of host IL-21 and HTLV-I Tax and proviral load (PVL) was evaluated to understand the role and mechanism of IL-21 in HTLV-1 infections and the subsequent development of HAM/TSP...
April 4, 2017: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/28373876/il-21-receptor-antagonist-inhibits-differentiation-of-b-cells-toward-plasmablasts-upon-alloantigen-stimulation
#10
Kitty de Leur, Frank J M F Dor, Marjolein Dieterich, Luc J W van der Laan, Rudi W Hendriks, Carla C Baan
Interaction between T follicular helper (Tfh) cells and B cells is complex and involves various pathways, including the production of IL-21 by the Tfh cells. Secretion of IL-21 results in B cell differentiation toward immunoglobulin-producing plasmablasts. In patients after kidney transplantation, the formation of alloantibodies produced by donor antigen-activated B cells are a major cause of organ failure. In this allogeneic response, the role of IL-21-producing Tfh cells that regulate B cell differentiation is unknown...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28364628/human-adipose-tissue-derived-mesenchymal-stem-cells-in-rheumatoid-arthritis-regulatory-effects-on-peripheral-blood-mononuclear-cells-activation
#11
Rasoul Baharlou, Abbas Ahmadi-Vasmehjani, Fatemeh Faraji, Mohammad Reza Atashzar, Mahshid Khoubyari, Salma Ahi, Saiedeh Erfanian, Shadi-Sadat Navabi
BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) are multipotent adult stem cells with immunomodulatory properties. The mechanisms by which MSCs inhibit the proliferation of pro-inflammatory T cells have not been fully elucidated yet. It is assumed that pro-inflammatory T-cells play an important role in the development of autoimmune diseases. We investigated the potential therapeutic effects of human adipose tissue derived (Ad)-MSCs on the peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients and healthy individuals, with a particular focus on Th17-associated cytokines...
March 29, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28360886/increased-circulating-t-follicular-helper-cells-are-inhibited-by-rituximab-in-neuromyelitis-optica-spectrum-disorder
#12
Cong Zhao, Hong-Zeng Li, Dai-Di Zhao, Chao Ma, Fang Wu, Ya-Nan Bai, Min Zhang, Zhu-Yi Li, Jun Guo
Neuromyelitis optica spectrum disorder (NMOSD) is a severe autoimmune disease of the central nervous system. The existence of autoantibody targeting aquaporin-4 (AQP4-Ab) indicates the involvement of humoral immunity in the pathogenesis of this disease. Rituximab (RTX), a monoclonal antibody against CD20, has been used to treat NMOSD by depleting circulating B cells and overall satisfactory outcome has been achieved. Although T follicular helper cells have been proved to regulate B cell activation and antibody production, the role of these cells in NMOSD and the impact of RTX treatment on these cells remain less understood...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28358365/madecassic-acid-the-contributor-to-the-anti-colitis-effect-of-madecassoside-enhances-the-shift-of-th17-toward-treg-cells-via-the-ppar%C3%AE-ampk-acc1-pathway
#13
Xiaotian Xu, Yuhui Wang, Zhifeng Wei, Wenhui Wei, Peng Zhao, Bei Tong, Yufeng Xia, Yue Dai
The imbalance between Th17 and Treg cells substantially contributes to the intestinal immune disturbance and subsequent tissue injury in ulcerative colitis. The triterpenoid-rich fraction of Centella asiatica was able to ameliorate dextran sulfate sodium-induced colitis in mice. Here we explored its active ingredient and underlying mechanism with a focus on restoring the Th17/Treg balance. The four main triterpenoids occurring in C. asiatica were shown to attenuate colitis in mice by oral administration. The most effective ingredient madecassoside lost anti-colitis effect when applied topically in the colon, and madecassic acid was recognized to be the active form of madecassoside...
March 30, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28346408/gut-microbial-metabolites-limit-the-frequency-of-autoimmune-t-cells-and-protect-against-type-1-diabetes
#14
Eliana Mariño, James L Richards, Keiran H McLeod, Dragana Stanley, Yu Anne Yap, Jacinta Knight, Craig McKenzie, Jan Kranich, Ana Carolina Oliveira, Fernando J Rossello, Balasubramanian Krishnamurthy, Christian M Nefzger, Laurence Macia, Alison Thorburn, Alan G Baxter, Grant Morahan, Lee H Wong, Jose M Polo, Robert J Moore, Trevor J Lockett, Julie M Clarke, David L Topping, Leonard C Harrison, Charles R Mackay
Gut dysbiosis might underlie the pathogenesis of type 1 diabetes. In mice of the non-obese diabetic (NOD) strain, we found that key features of disease correlated inversely with blood and fecal concentrations of the microbial metabolites acetate and butyrate. We therefore fed NOD mice specialized diets designed to release large amounts of acetate or butyrate after bacterial fermentation in the colon. Each diet provided a high degree of protection from diabetes, even when administered after breakdown of immunotolerance...
May 2017: Nature Immunology
https://www.readbyqxmd.com/read/28346226/a-tlr9-dependent-checkpoint-governs-b-cell-responses-to-dna-containing-antigens
#15
Vishal J Sindhava, Michael A Oropallo, Krishna Moody, Martin Naradikian, Lauren E Higdon, Lin Zhou, Arpita Myles, Nathaniel Green, Kerstin Nündel, William Stohl, Amanda M Schmidt, Wei Cao, Stephanie Dorta-Estremera, Taku Kambayashi, Ann Marshak-Rothstein, Michael P Cancro
Mature B cell pools retain a substantial proportion of polyreactive and self-reactive clonotypes, suggesting that activation checkpoints exist to reduce the initiation of autoreactive B cell responses. Here, we have described a relationship among the B cell receptor (BCR), TLR9, and cytokine signals that regulate B cell responses to DNA-containing antigens. In both mouse and human B cells, BCR ligands that deliver a TLR9 agonist induce an initial proliferative burst that is followed by apoptotic death. The latter mechanism involves p38-dependent G1 cell-cycle arrest and subsequent intrinsic mitochondrial apoptosis and is shared by all preimmune murine B cell subsets and CD27- human B cells...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28344884/the-differentiation-and-plasticity-of-tc17-cells-are-regulated-by-ctla-4-mediated-effects-on-stats
#16
Aditya Arra, Holger Lingel, Benno Kuropka, Jonas Pick, Tina Schnoeder, Thomas Fischer, Christian Freund, Mandy Pierau, Monika C Brunner-Weinzierl
As the blockade of inhibitory surface-molecules such as CTLA-4 on T cells has led to recent advances in antitumor immune therapy, there is great interest in identifying novel mechanisms of action of CD8(+) T cells to evoke effective cytotoxic antitumor responses. Using in vitro and in vivo models, we investigated the molecular pathways underlying the CTLA-4-mediated differentiation of IL-17-producing CD8(+) T cells (Tc17 cells) that strongly impairs cytotoxicity. Our studies demonstrate that Tc17 cells lacking CTLA-4 signaling have limited production of STAT3-target gene products such as IL-17, IL-21, IL-23R and RORγt...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344863/tumor-infiltrating-lymphocytes-tils-from-patients-with-glioma
#17
Zhenjiang Liu, Qingda Meng, Jiri Bartek, Thomas Poiret, Oscar Persson, Lalit Rane, Elena Rangelova, Christopher Illies, Inti Harvey Peredo, Xiaohua Luo, Martin Vijayakumar Rao, Rebecca Axelsson Robertson, Ernest Dodoo, Markus Maeurer
Tumor-infiltrating lymphocytes (TILs) may represent a viable source of T cells for the biological treatment of patients with gliomas. Glioma tissue was obtained from 16 patients, tumor cell lines were established, and TILs were expanded in 16/16 cases using a combination of IL-2/IL-15/IL-21. Intracellular cytokine staining (ICS, IL-2, IL-17, TNFα and IFNγ production) as well as a cytotoxicity assay was used to detect TIL reactivity against autologous tumor cells or shared tumor-associated antigens (TAAs; i...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344062/il-21-may-promote-granzyme-b-dependent-nk-plasmacytoid-dendritic-cell-functional-interaction-in-cutaneous-lupus-erythematosus
#18
Valentina Salvi, William Vermi, Andrea Cavani, Silvia Lonardi, Teresa Carbone, Fabio Facchetti, Daniela Bosisio, Silvano Sozzani
Autoimmune skin lesions are characterized by a complex cytokine milieu and by the accumulation of plasmacytoid dendritic cells (pDCs). Granzyme B (GrB) transcript is abundant in activated pDCs, though its mechanisms of regulation and biological role are largely unknown. Here we report that IL-21 was the only Th1/Th17 cytokine able to induce the expression and secretion of GrB by pDCs and that this action was counteracted by the autocrine production of type I interferons (IFNs). In lupus erythematosus (LE) skin lesions, the percentage of GrB(+) pDCs directly correlated with the IL-21/MxA ratio, indicating that the interplay between these two cytokines finely tune the levels of pDC-dependent GrB also in vivo...
March 23, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28337387/pro-and-anti-inflammatory-cytokines-in-children-with-malaria-in-franceville-gabon
#19
Sandrine Lydie Oyegue-Liabagui, Aline Gaëlle Bouopda-Tuedom, Lady Charlène Kouna, Sydney Maghendji-Nzondo, Herman Nzoughe, Nina Tchitoula-Makaya, Irene Pegha-Moukandja, Jean-Bernard Lekana-Douki
Severe Plasmodium falciparum malaria anemia (SMA) is a major cause of mortality in pediatric wards. Variations in inflammatory mediator production play an essential role in disease outcomes. Indeed, several studies have shown the involvement of pro- and anti-inflammatory cytokines such as IFN-γ, IL-6, TNF-α and IL-10 in malaria immunopathology. In other hand the exact role of Th17 cytokines such as IL-17, IL-22 and IL-21 in malaria remains poorly documented. Here, we investigated IFN-γ, TNF-α, IL-6, IL-12, IL-10, IL-4, IL-13, IL-17, IL-22 and IL-21 circulating levels and their association with malaria anemia and parasitemia in Gabonese children...
2017: American Journal of Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28314758/immune-checkpoint-dysfunction-in-medium-and-large-vessel-vasculitis
#20
Ryu Watanabe, Hui Zhang, Gerald Berry, Jorg J Goronzy, Cornelia M Weyand
Giant cell arteritis (GCA) is a granulomatous vasculitis of the aorta and its medium-sized branch vessels. CD4 T-cells, macrophages and dendritic cells build granulomatous infiltrates that injure the vessel wall and elicit a maladaptive response-to-injury. Pathologic consequences include fragmentation of elastic membranes, destruction of the medial layer, microvascular neoangiogenesis, massive outgrowth of myofibroblasts, and lumen-occlusive intimal hyperplasia. Antigens have been suspected to drive the local activation of vasculitogenic CD4 T-cells, but recent data suggest a more generalized defect in the threshold setting of such T-cells, rendering them hyperreactive...
March 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
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