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IL-21

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https://www.readbyqxmd.com/read/28197386/deficiency-of-the-immunostimulatory-cytokine-il-21-promotes-intestinal-neoplasia-via-dysregulation-of-the-th1-th17-axis
#1
Mia Shapiro, Bisweswar Nandi, Gabriel Gonzalez, Rao H Prabhala, Hiroshi Mashimo, Qin Huang, Natasha Y Frank, Nikhil C Munshi, Jason S Gold
IL-21 has reported activity in promoting both Th1 and Th17 immune responses. Its role in sporadic human colorectal cancer is unknown. We aimed to delineate the role of IL-21 in a model of sporadic intestinal carcinogenesis. We found that in APC(MIN/+) mice, ablation of IL-21 increased intestinal tumorigenesis. Expression of pro-inflammatory Th17-associated genes, including RORγt and IL-17A, was increased in the intestine in the absence of IL-21, while expression of antitumor Th1-associated genes Tbet, IFNγ, granzyme B, and perforin was decreased...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28194154/the-role-of-cd4-t-follicular-helper-cells-in-hiv-infection-from-the-germinal-center-to-the-periphery
#2
REVIEW
John Patrick Thornhill, Sarah Fidler, Paul Klenerman, John Frater, Chansavath Phetsouphanh
T follicular helper cells (TFh) are key components of the adaptive immune system; they are primarily found in germinal centers (GCs) where their interaction with B cells supports humoral immune responses and efficient antibody production. They are defined by the expression of CXC receptor 5, program death-1, ICOS, and secretion of IL-21. Their differentiation is regulated by B-cell lymphoma 6. The relationship and function of circulating TFh to bona fide TFh resident in the GC is much debated. HIV infection impacts the TFh response with evidence of aberrant TFh function observed in acute and chronic infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28189042/activity-of-inflammatory-bowel-disease-influences-the-expression-of-cytokines-in-gingival-tissue
#3
C M Figueredo, A P Martins, R Lira-Junior, J B Menegat, A T Carvalho, R G Fischer, A Gustafsson
This study assessed the cytokine expression in gingival and intestinal tissues from periodontitis patients with inflammatory bowel disease (IBD) and evaluated if IBD activity is a covariate to the amount of gingival cytokines. Paired gingival and intestinal tissues were collected from 21 patients and homogenised using a cell disruptor. Cytokine expression (IL-1β, IL-4, IL-6, IL-10, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IL-17A, IL-17F, IFN-γ, sCD40L, and TNF-α) was evaluated using bead-based multiplex technology...
February 8, 2017: Cytokine
https://www.readbyqxmd.com/read/28169240/synergistic-induction-of-apoptosis-in-b-cell-chronic-lymphocytic-leukemia-cells-after-treatment-with-all-trans-retinoic-acid-in-combination-with-interleukin-21-and-rituximab
#4
Kazem Abbaszadeh-Goudarzi, Fazel Shokri, Mostafa Hosseini, Farhad Jadidi-Niaragh, Ghasem Ghalamfarsa, Ali Akbar Saboor-Yaraghi
AIM: B-cell chronic lymphocytic leukemia (B-CLL) is the most common adult leukemia in the Western world and characterized by the progressive expansion of malignant B lymphocytes in peripheral blood. In spite of advances in sciences to recognize the number of effective agents for the treatment of chronic lymphocytic leukemia (CLL), this leukemia is thought as incurable one. Introducing a new therapy that has a direct effect on B-CLL lymphocytes and no cytotoxic effects on the other cells is a great wish...
October 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28165883/the-role-of-il-23-in-the-treatment-of-psoriasis
#5
Lluís Puig
The IL-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis. Human IL-23 is primarily produced by antigen-presenting cells and induces and maintains differentiation of Th17 cells and Th22 cells, a primary cellular source of proinflammatory cytokines such as IL-17 and IL-22, which mediate the epidermal hyperplasia, keratinocyte immune activation and tissue inflammation inherent in psoriasis. Agents that target the p40 subunit common to both IL-12 and IL-23 have shown robust clinical activity, but selectivity for IL-23p19 could offer advantages in efficacy and safety with respect to anti-p40 blockade...
February 6, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28162181/-effect-of-serum-interleukin-21-on-b-cell-secretory-capacity-and-apoptosis-in-patients-with-systemic-lupus-erythematosus
#6
L T Zheng, L D Zhao, C Zhao, Y Zhao, X Zhang, F C Zhang, X F Zeng, F L Tang, X You
Objective: To investigate the secretory capacity and apoptosis of interleukin (IL)-21 induced normal B cells by co-culture with serum from patients with systemic lupus erythematosus (SLE). Methods: Serum from twenty new-onset SLE patients and 20 healthy donors were collected. CD(19)(+) B cells from the normal controls were co-cultured with serum from SLE patients in the presence or absence of IL-21-R-FC(4 μg/ml). Supernatant IgG and IgM concentration were measured by immunoturbidimetric assay on day 5. Supernatant anti-dsDNA level was determined by ELISA...
February 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/28158305/higher-efficacy-of-anti-il-6-il-21-combination-therapy-compared-to-monotherapy-in-the-induction-phase-of-th17-driven-experimental-arthritis
#7
Debbie M Roeleveld, Renoud J Marijnissen, Birgitte Walgreen, Monique M Helsen, Liduine van den Bersselaar, Fons A van de Loo, Peter L van Lent, Peter M van der Kraan, Wim B van den Berg, Marije I Koenders
Th17 cells and their cytokines are linked to the pathogenesis of rheumatoid arthritis, a chronic autoimmune disease characterized by joint inflammation. Th17 development is initiated by combined signaling of TGF-β and IL-6 or IL-21, and can be reduced in the absence of either IL-6 or IL-21. The aim of this study was to assess whether combinatorial IL-6/IL-21 blockade would more potently inhibit Th17 development, and be more efficacious in treating arthritis than targeting either cytokine. We assessed in vitro Th17 differentiation efficacy in the absence of IL-6 and/or IL-21...
2017: PloS One
https://www.readbyqxmd.com/read/28157399/cxcr5-cd8-t-cells-indirectly-offer-b-cell-help-and-are-inversely-correlated-with-viral-load-in-chronic-hepatitis-b-infection
#8
Hang Jiang, Linhai Li, Jiang Han, Zhiwei Sun, Yihui Rong, Yun Jin
Treatment options for chronic hepatitis B (CHB) infection are extremely limited. CXCR5(+) CD8(+) T cell is a novel cell subtype and could possess strong cytotoxic properties in HIV infection. In this study, we investigated the role of CXCR5(+) CD8(+) T cells in CHB patients. Compared to healthy individuals, both CHB patients and hepatitis B virus (HBV)-infected hepatocellular carcinoma patients presented significant upregulation of CXCR5(+) CD8(+) T cells in peripheral blood, in which CXCR5(+) CD8(+) T cells were negatively correlated with the frequency of CXCR5(+) CD4(+) T cells in CHB patients...
February 3, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28153782/rapid-de-novo-generation-of-antigen-specific-human-b-cells-with-expression-of-blimp-1-and-aid-by-in-vitro-immunization
#9
Xu Fang, Yue Tong, Hong Tian, Hongyu Ning, Xiangdong Gao, Wenbing Yao
In vitro immunization with antigens and cytokines triggers specific human B-cell response in short periods and is therefore superior to conventional in vivo immunization for antibody development. However, this new technology is limited by low efficiency, poor reproducibility, and requirement of pre-immunized lymphocytes. In this study, we demonstrate a novel method for de novo inducing antigen-specific human B cells in vitro. Unlike previous in vitro immunization of unfractionated PBMCs, we firstly optimized the conditions for inducing monocyte-derived dendritic cells (DCs) to efficiently capture, process, and present antigens...
January 30, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28150777/pathologically-expanded-peripheral-t-helper-cell-subset-drives-b-cells-in-rheumatoid-arthritis
#10
Deepak A Rao, Michael F Gurish, Jennifer L Marshall, Kamil Slowikowski, Chamith Y Fonseka, Yanyan Liu, Laura T Donlin, Lauren A Henderson, Kevin Wei, Fumitaka Mizoguchi, Nikola C Teslovich, Michael E Weinblatt, Elena M Massarotti, Jonathan S Coblyn, Simon M Helfgott, Yvonne C Lee, Derrick J Todd, Vivian P Bykerk, Susan M Goodman, Alessandra B Pernis, Lionel B Ivashkiv, Elizabeth W Karlson, Peter A Nigrovic, Andrew Filer, Christopher D Buckley, James A Lederer, Soumya Raychaudhuri, Michael B Brenner
CD4(+) T cells are central mediators of autoimmune pathology; however, defining their key effector functions in specific autoimmune diseases remains challenging. Pathogenic CD4(+) T cells within affected tissues may be identified by expression of markers of recent activation. Here we use mass cytometry to analyse activated T cells in joint tissue from patients with rheumatoid arthritis, a chronic immune-mediated arthritis that affects up to 1% of the population. This approach revealed a markedly expanded population of PD-1(hi)CXCR5(-)CD4(+) T cells in synovium of patients with rheumatoid arthritis...
1, 2017: Nature
https://www.readbyqxmd.com/read/28149833/assessment-of-the-link-between-in-utero-exposure-to-2-aminoanthracene-2aa-and-type-1-diabetes-t1d
#11
Christopher A Mays, Daniel A Hunter, Wilson Yau, Worlanyo E Gato
BACKGROUND: A recent diabetes report revealed an increased incidence in diabetes including type 1-diabetes (T1D). The increase in the numbers of T1D incidences are thought to be related to environmental reasons such as the exposure to environmental chemicals including arylamine 2-aminoanthracene (2AA). T1D is an autoimmune disease of the pancreatic islet in which insulin-producing beta cells are destroyed by auto-reactive T-cells and monocytic cells. METHODS: The purpose of this study is to examine the extent to which 2AA exposure contributes to T1D...
2017: Journal of Diabetes and Metabolic Disorders
https://www.readbyqxmd.com/read/28149160/immune-characteristics-study-of-ag490-a-signal-pathway-inhibitor-in-eae-model-mice
#12
Zhihua Zhao, Zhifeng Mao, Junjie Yin, Yaqing Shu, Wei Qiu, Zhengqi Lu, Xueqiang Hu
Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination, axonal damage and progressive neurologic dysfunction in central nervous system (CNS). Many evidences show that B cells play an important role in the pathogenesis of MS. Follicular helper T cells (Tfh) secrete IL-21 to prompt the proliferation and differentiation of B cells in germinal center (GC) through clonal proliferation, somatic hypermutation, antibody class switching, antibody affinity maturation process. AG490 is a synthetic inhibitor to JAK-STAT signal pathway, which has been studied in inflammatory, tumor and autoimmune diseases...
February 2017: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/28146052/expansion-of-t-cells-with-interleukin-21-for-adoptive-immunotherapy-of-murine-mammary-carcinoma
#13
Christine K Zoon, Wen Wan, Laura Graham, Harry D Bear
We previously demonstrated that culturing antigen-sensitized draining lymph node (DLN) lymphocytes from BALB/c mice in interleukin (IL)-7/15 after activation with bryostatin/ionomycin (B/I) is superior to culture in IL-2 for expansion, differentiation to cluster of differentiation (CD)8+ cells and anti-tumor activity. We sought to determine whether the substitution or addition of IL-21 to culture had a similar effect. DLN lymphocytes were antigen-sensitized with 4T1 mammary carcinoma 10 days prior to harvest, activated with B/I, and expanded in culture for 7 days with either IL-2, IL-21, IL-2/21, IL-7/15, or IL-7/15/21...
January 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28141856/transcriptional-profiling-in-experimental-visceral-leishmaniasis-reveals-a-broad-splenic-inflammatory-environment-that-conditions-macrophages-toward-a-disease-promoting-phenotype
#14
Fanping Kong, Omar A Saldarriaga, Heidi Spratt, E Yaneth Osorio, Bruno L Travi, Bruce A Luxon, Peter C Melby
Visceral Leishmaniasis (VL), caused by the intracellular protozoan Leishmania donovani, is characterized by relentlessly increasing visceral parasite replication, cachexia, massive splenomegaly, pancytopenia and ultimately death. Progressive disease is considered to be due to impaired effector T cell function and/or failure of macrophages to be activated to kill the intracellular parasite. In previous studies, we used the Syrian hamster (Mesocricetus auratus) as a model because it mimics the progressive nature of active human VL...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28140446/the-proportion-of-different-il-17-producing-t-cell-subsets-is-associated-with-liver-fibrosis-in-chronic-hepatitis-c
#15
Fabio C O F Cachem, Aleida S O Dias, Clarice Monteiro, José Roberto Castro, Gabriel Fernandes, Letícia Delphim, Adilson J Almeida, Felipe Tavares, Alessandra M A Maciel, Marcia M Amendola-Pires, Carlos E Brandão-Mello, Cleonice A M Bento
Studies have suggested the pivotal role of Th1-related cytokines on the outcome of HCV infection. Nevertheless, the role of different IL-17-secreting T cells on chronic hepatitis C (CHC) is less clear. Here, the in vivo IL-1β, IL-6, and IL-17 levels were positively correlated with both alanine aminotransferase (ALT) levels and hepatic lesions. When compared with the control group, CHC patients showed lower proportion of IL-17-secreting (CD4(+) and CD8(+) ) T cells capable of simultaneously producing IL-21...
January 31, 2017: Immunology
https://www.readbyqxmd.com/read/28138558/circulating-cxcr5-cxcr3-pd-1-lo-tfh-like-cells-in-hiv-1-controllers-with-neutralizing-antibody-breadth
#16
Enrique Martin-Gayo, Jacqueline Cronin, Taylor Hickman, Zhengyu Ouyang, Madelene Lindqvist, Kellie E Kolb, Julian Schulze Zur Wiesch, Rafael Cubas, Filippos Porichis, Alex K Shalek, Jan van Lunzen, Elias K Haddad, Bruce D Walker, Daniel E Kaufmann, Mathias Lichterfeld, Xu G Yu
HIV-1-specific broadly neutralizing antibodies (bnAbs) typically develop in individuals with continuous high-level viral replication and increased immune activation, conditions that cannot be reproduced during prophylactic immunization. Understanding mechanisms supporting bnAb development in the absence of high-level viremia may be important for designing bnAb-inducing immunogens. Here, we show that the breadth of neutralizing antibody responses in HIV-1 controllers was associated with a relative enrichment of circulating CXCR5(+)CXCR3(+)PD-1(lo) CD4(+) T cells...
January 26, 2017: JCI Insight
https://www.readbyqxmd.com/read/28138156/antibody-dependent-cell-cytotoxicity-adcc-immunotherapy-strategies-enhancing-effector-nk-cells
#17
REVIEW
Maria Carmen Ochoa, Luna Minute, Inmaculada Rodriguez, Saray Garasa, Elisabeth Perez-Ruiz, Susana Inogés, Ignacio Melero, Pedro Berraondo
Antibody-dependent cellular cytotoxicity (ADCC) is a set of mechanisms that target cells coated with IgG antibodies of the proper subclasses (IgG1 in the human) to be the prey of cell-to-cell cytolysis executed by immune cells expressing FcRIIIA (CD16A). These effectors include not only NK cells but also other CD16(+) subsets such as monocyte/macrophages, NKT cells or γδ T cells. In cancer therapy, ADCC is exploited by antibodies that selectively recognize proteins on the surface of malignant cells. An approach to enhance antitumor activity is to act on effector cells so they are increased in their numbers or enhanced in their individual (on a cell per cell basis) ADCC performance...
January 31, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28137826/anti-cd20-interleukin-21-fusokine-targets-malignant-b-cells-via-direct-apoptosis-and-nk-cell-dependent-cytotoxicity
#18
Shruti Bhatt, Salma Parvin, Yu Zhang, Hyun-Mi Cho, Kranthi Kunkalla, Francisco Vega, John M Timmerman, Seung-Uon Shin, Joseph D Rosenblatt, Izidore S Lossos
In spite of newly emerging therapies and the improved survival of non-Hodgkin lymphoma (NHL) patients, relapses or primary refractory disease are commonly observed and associated with dismal prognosis. While discovery of the anti-CD20 antibody rituximab has markedly improved outcomes in B-cell NHL, rituximab resistance remains an important obstacle to successful treatment of these tumors. To improve the efficacy of CD20-targeted therapy, we fused IL-21, which induces direct lymphoma cytotoxicity and activates immune effector cells, to the anti-CD20 antibody (αCD20-IL-21 fusokine)...
January 30, 2017: Blood
https://www.readbyqxmd.com/read/28128370/an-ocular-protein-triad-can-classify-four-complex-retinal-diseases
#19
J J W Kuiper, L Beretta, S Nierkens, R van Leeuwen, N H Ten Dam-van Loon, J Ossewaarde-van Norel, M C Bartels, J D F de Groot-Mijnes, P Schellekens, J H de Boer, T R D J Radstake
Retinal diseases generally are vision-threatening conditions that warrant appropriate clinical decision-making which currently solely dependents upon extensive clinical screening by specialized ophthalmologists. In the era where molecular assessment has improved dramatically, we aimed at the identification of biomarkers in 175 ocular fluids to classify four archetypical ocular conditions affecting the retina (age-related macular degeneration, idiopathic non-infectious uveitis, primary vitreoretinal lymphoma, and rhegmatogenous retinal detachment) with one single test...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28125840/association-of-high-mobility-group-box-1-with-th-cell-related-cytokines-in-the-vitreous-of-ocular-sarcoidosis-patients
#20
Masaru Takeuchi, Manzo Taguchi, Tomohito Sato, Kyoko Karasawa, Yutaka Sakurai, Kohzou Harimoto, Masataka Ito
Purpose: High-mobility group box-1 (HMGB1) is a nonhistone DNA-binding nuclear protein released from necrotic cells, which is also secreted by activated leukocytes and acts as a primary proinflammatory cytokine. In this study, we compared vitreous HMGB1 levels in ocular sarcoidosis with those in noninflammatory vitreoretinal diseases and evaluated its association with Th cell-related and proinflammatory cytokines. Methods: The study group consisted of 24 patients with ocular sarcoidosis...
January 1, 2017: Investigative Ophthalmology & Visual Science
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