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Shai S Shen-Orr, David Furman, Brian A Kidd, Francois Hadad, Patricia Lovelace, Ying-Wen Huang, Yael Rosenberg-Hasson, Sally Mackey, Fatemeh A Gomari Grisar, Yishai Pickman, Holden T Maecker, Yueh-Hsiu Chien, Cornelia L Dekker, Joseph C Wu, Atul J Butte, Mark M Davis
Chronic inflammation, a decline in immune responsiveness, and reduced cardiovascular function are all associated with aging, but the relationships among these phenomena remain unclear. Here, we longitudinally profiled a total of 84 signaling conditions in 91 young and older adults and observed an age-related reduction in cytokine responsiveness within four immune cell lineages, most prominently T cells. The phenotype can be partially explained by elevated baseline levels of phosphorylated STAT (pSTAT) proteins and a different response capacity of naive versus memory T cell subsets to interleukin 6 (IL-6), interferon α (IFN-α), and, to a lesser extent, IL-21 and IFN-γ...
October 12, 2016: Cell Systems
Maria C Lebre, Pedro L Vieira, Man Wai Tang, Saïda Aarrass, Boy Helder, Thomas Newsom-Davis, Paul P Tak, Gavin R Screaton
Bone and cartilage destruction is one of the key manifestations of rheumatoid arthritis (RA). Although the role of T helper (Th)17 cells in these processes is clear, the role of IL-21-producing cells T cells has been neglected. We sought to investigate the role of IL-21 in RA by focusing on the functional characteristics of the main producers of this cytokine, synovial CD4(+)IL-21(+) T cells. We show that the frequency of both synovial fluid (SF) CD4(+)IL-21(+) or CD4(+)IL-21(+)TNF(+) T cells in patients with RA was significantly higher compared with patients with psoriatic arthritis (PsA)...
October 12, 2016: Journal of Leukocyte Biology
Wang-Dong Xu, Lin-Chong Su, Qi-Bing Xie, Yi Zhao, Yi Liu
BACKGROUND: Interleukin-2 inducible T-cell kinase (ITK) is expressed in T cells, and plays an important role in autoimmune inflammatory diseases through regulating the balance of Th17/Treg. However, its role in human systemic lupus erythematosus (SLE) remains unclear. The present study aims to measure the activation status of ITK in T cells from SLE patients and healthy controls, and identify its possible correlation to disease severity. We also discuss the serum levels of Th17, Treg related cytokines including IL-17, IL-21, IL-22, IL-10, analyzing correlation between ITK and Th17/Treg related cytokines...
October 8, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
Chenggen Xiao, Qiaoling Zhou, Xiaozhao Li, Hui Li, Ting Meng, Yong Zhong, Jiaxi Pu, Mengyuan Zhu, Yan Xu, Lu Gan, Hong Sun, Ping Xiao
IL-22-producing helper T cells (Th22 cells) have been reported to be involved in lgA nephropathy. However, the mechanisms underlying the differentiation and immune regulation of Th22 cells in lgA nephropathy remain unknown. To elucidate the mechanisms by which Th22 cells differentiate and are recruited into the kidney in lgA nephropathy, the distribution of Th22 cells in both the kidney and blood was determined. Additionally, the impacts of proinflammatory cytokines and antigen presentation in the kidney on Th22 cell differentiation were explored...
2016: American Journal of Translational Research
Leigh Jones, Wen Qi Ho, Sze Ying, Lakshmi Ramakrishna, Kandhadayar G Srinivasan, Marina Yurieva, Wan Pei Ng, Sharrada Subramaniam, Nur H Hamadee, Sabrina Joseph, Jayashree Dolpady, Koji Atarashi, Kenya Honda, Francesca Zolezzi, Michael Poidinger, Juan J Lafaille, Maria A Curotto de Lafaille
No abstract text is available yet for this article.
October 10, 2016: Scientific Reports
Ravendra Garg, Michael Theaker, Elisa C Martinez, Sylvia van Drunen Littel-van den Hurk
Respiratory syncytial virus (RSV) causes serious respiratory illness in infants and elderly. RSV infection induces short-lived immunity, which leaves people prone to re-infection. In contrast, the RSV fusion (F) protein formulated with a novel adjuvant (∆F/TriAdj) elicits long term protective immunity. A comparison of RSV-immunized mice to mice vaccinated with a single dose of ∆F/TriAdj showed no difference in IgG1 and IgG2a production; however, local IgA secreting memory B cell development and B cell IgA production were significantly lower in RSV vaccinated mice than in ∆F/TriAdj-immunized mice...
October 6, 2016: Virology
Sheikh Fayaz Ahmad, Mushtaq Ahmad Ansari, Ahmed Nadeem, Khairy M A Zoheir, Saleh A Bakheet, Abdulaziz M S Alsaad, Othman A Al-Shabanah, Sabry M Attia
We set out to investigate the influence of STA-21, a dynamic STAT-3 inhibitor, on the expansion and progression of rheumatoid arthritis (RA), and to determine its potential mechanisms of action in a mouse model of collagen antibody-induced arthritis (CAIA). To this end, arthritis was induced via intravenous (IV) injection of Balb/c mice with a cocktail of antibodies directed against type II collagen (1.5μg/mouse, IV), followed by lipopolysaccharide (LPS) at a dose of (25μg/mouse, i.p.) on day 3. Mice were then left untreated or were simultaneously treated with STA-21 (0...
October 3, 2016: Immunobiology
Brodie Miles, Shannon M Miller, Joy M Folkvord, David N Levy, Eva G Rakasz, Pamela J Skinner, Elizabeth Connick
During chronic HIV infection, viral replication is concentrated in secondary lymphoid follicles. Cytotoxic CD8 T cells control HIV replication in extrafollicular regions, but not in the follicle. Here, we show CXCR5hiCD44hiCD8 T cells are a regulatory subset differing from conventional CD8 T cells, and constitute the majority of CD8 T cells in the follicle. This subset, CD8 follicular regulatory T cells (CD8 TFR), expand in chronic SIV infection, exhibit enhanced expression of Tim-3 and IL-10, and express less perforin compared to conventional CD8 T cells...
October 2016: PLoS Pathogens
Mahmoud Sadeghi, Imad Lahdou, Gerhard Opelz, Arianeb Mehrabi, Martin Zeier, Paul Schnitzler, Volker Daniel
BACKGROUND: Cytomegalovirus seropositivity is an independent risk factor for atherosclerosis in patients with ESRD. Donor CMV seropositivity is associated with higher graft loss. Dendritic cells, macrophages and Th17 lymphocytes are defined as producers of IL-23. IL-23 is thought to be involved in the promotion of Th17 cell polarization. Latent CMV-induced Th17 might be involved in the pathogenesis of CMV infection in patients with ESRD. We aimed to evaluate associations of Th17-dependent cytokines with ESRD, CMV status and post-transplant outcome in kidney transplantation...
October 3, 2016: BMC Immunology
Michel Varrin-Doyer, Kara L Pekarek, Collin M Spencer, Claude C A Bernard, Raymond A Sobel, Bruce A C Cree, Ulf Schulze-Topphoff, Scott S Zamvil
OBJECTIVE: To evaluate the influence of oral laquinimod, a candidate multiple sclerosis (MS) treatment, on induction of T follicular helper cells, development of meningeal B cell aggregates, and clinical disease in a spontaneous B cell-dependent MS model. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by immunization with recombinant myelin oligodendrocyte glycoprotein (rMOG) protein. Spontaneous EAE was evaluated in C57BL/6 MOG p35-55-specific T cell receptor transgenic (2D2) × MOG-specific immunoglobulin (Ig)H-chain knock-in (IgH(MOG-ki) [Th]) mice...
October 2016: Neurology® Neuroimmunology & Neuroinflammation
Tue Kruse Rasmussen
Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are lifelong diseases with increased mortality and chronic pains. They are both characterized by immunological imbalances causing the immune system attack and destroy the bodies own tissues (called autoimmune disease). The best treatment, we are currently able to offer these patients, cause significant side-effects and can not prevent significant loss of quality of life. At the heart of the disease mechanisms in RA and SLE are subsets of immune cells called T and B cells...
October 2016: Danish Medical Journal
Catherine W Cai, Jennifer R Blase, Xiuli Zhang, Christopher S Eickhoff, Daniel F Hoft
Th17 cells are a subset of CD4+ T cells known to play a central role in the pathogenesis of many autoimmune diseases, as well as in the defense against some extracellular bacteria and fungi. However, Th17 cells are not believed to have a significant function against intracellular infections. In contrast to this paradigm, we have discovered that Th17 cells provide robust protection against Trypanosoma cruzi, the intracellular protozoan parasite that causes Chagas disease. Th17 cells confer significantly stronger protection against T...
October 2016: PLoS Pathogens
Peter T Sage, Noga Ron-Harel, Vikram R Juneja, Debattama R Sen, Seth Maleri, Waradon Sungnak, Vijay K Kuchroo, W Nicholas Haining, Nicolas Chevrier, Marcia Haigis, Arlene H Sharpe
Follicular regulatory T cells (TFR cells) inhibit follicular helper T cell (TFH cell)-mediated antibody production. The mechanisms by which TFR cells exert their key immunoregulatory functions are largely unknown. Here we found that TFR cells induced a distinct suppressive state in TFH cells and B cells, in which effector transcriptional signatures were maintained but key effector molecules and metabolic pathways were suppressed. The suppression of B cell antibody production and metabolism by TFR cells was durable and persisted even in the absence of TFR cells...
October 3, 2016: Nature Immunology
Shimeng Luo, Yun Li, Yingpei Li, Qixing Zhu, Jianhua Jiang, Changhao Wu, Tong Shen
Increasing evidence demonstrates that perinatal exposure to Bisphenol A (BPA) can cause immune disorders throughout the life span. However, the biological basis for these immune disorders is poorly understood and the effects of exposure to BPA on Th17 development are unknown. The present study sought to characterize alterations of Th17 cells in childhood and adulthood following gestational and lactational exposure to environmentally relevant low-dose of BPA and the underlying mechanisms. Pregnant dams were exposed to BPA (10, 100 or 1000nM) via drinking water from gestational day (GD) 0 to postnatal day (PND) 21...
September 26, 2016: Environmental Toxicology and Pharmacology
Fleurieke Verhagen, Jonas Kuiper, Stefan Nierkens, S M Imhof, Timothy Radstake, Joke de Boer
OBJECTIVE: In this report we describe, for the first time, the activation of the peripheral immune compartment in a patient with a CRB1 linked retinal degenerative disease, masquerading as intermediate uveitis. METHODS: To monitor the immune system during systemic immunosuppressive treatment, given for the initial diagnosis of intermediate uveitis, blood samples were taken before and during therapy, for analysis of peripheral blood mononuclear cell-subsets and circulating immune mediators...
October 3, 2016: Expert Review of Clinical Immunology
Eliseo F Castillo, Handong Zheng, Christian Van Cabanlong, Fei Dong, Yan Luo, Yi Yang, Meilian Liu, Winston W-Y Kao, Xuexian O Yang
TH17 cells play an essential role in the development of both human multiple sclerosis and animal experimental autoimmune encephalomyelitis (EAE). Nevertheless, it is not well understood how the pathogenicity of TH17 cells is controlled in the autoimmune neuro-inflammation. In vitro, we found Lumican (Lum), an extracellular matrix protein, is selectively expressed by TH17 cells among tested murine TH subsets. Lum-deficiency leads to earlier onset and enhanced severity of experimental autoimmune encephalomyelitis...
September 29, 2016: European Journal of Immunology
Stefano Alivernini, Mariola Kurowska-Stolarska, Barbara Tolusso, Roberta Benvenuto, Aziza Elmesmari, Silvia Canestri, Luca Petricca, Antonella Mangoni, Anna Laura Fedele, Clara Di Mario, Maria Rita Gigante, Elisa Gremese, Iain B McInnes, Gianfranco Ferraccioli
MicroRNA-155 (miR-155) is an important regulator of B cells in mice. B cells have a critical role in the pathogenesis of rheumatoid arthritis (RA). Here we show that miR-155 is highly expressed in peripheral blood B cells from RA patients compared with healthy individuals, particularly in the IgD(-)CD27(-) memory B-cell population in ACPA(+) RA. MiR-155 is highly expressed in RA B cells from patients with synovial tissue containing ectopic germinal centres compared with diffuse synovial tissue. MiR-155 expression is associated reciprocally with lower expression of PU...
September 27, 2016: Nature Communications
Basile Lebailly, Francina Langa, Christian Boitard, Philip Avner, Ute Christine Rogner
Nonobese diabetic (NOD) mice are a model for type 1 diabetes that displays defects in central immune tolerance, including impairment of thymocyte apoptosis and proliferation. Thymocyte apoptosis is decreased in NOD/Lt mice compared to nondiabetic C3H/HeJ and C57BL/6 mice. Analysis of a set of NOD.C3H and NOD.B6 congenic mouse strains for distal chromosome 6 localizes the phenotype to the 700 kb Idd6.3 interval. Idd6.3 contains the type 1 diabetes candidate gene aryl hydrocarbon receptor nuclear translocator-like 2 (Arntl2), encoding a circadian rhythm-related transcription factor...
September 26, 2016: Mammalian Genome: Official Journal of the International Mammalian Genome Society
Rui Yang, April R Masters, Karen A Fortner, Devin P Champagne, Natalia Yanguas-Casás, Daniel J Silberger, Casey T Weaver, Laura Haynes, Mercedes Rincon
IL-6 is known to contribute to the differentiation of CD4(+) T cells into different subsets of effector T helper cells. Less is known about the potential of IL-6 in regulating CD8(+) T cell effector function. Here, we identify IL-6 as a master regulator of IL-21 in effector CD8(+) T cells. IL-6 promotes the differentiation of a subset of naive CD8(+) T cells that express IL-6R into a unique population of effector CD8(+) T cells characterized by the production of high levels of IL-21 and low levels of IFN-γ...
September 26, 2016: Journal of Experimental Medicine
Yalei Liu, Ran You, Nan Yu, Yan Gong, Chenxue Qu, Yang Zhang, Guizhi Lu, Youyuan Huang, Hong Zhang, Ying Gao, Yanming Gao, Xiaohui Guo
Both cellular and humoral responses play important roles in the pathogenesis of Hashimoto's thyroiditis (HT). However, the immunological differences between euthyroid (mild HT) and hypothyroid (severe HT) patients are unknown. This study aimed to investigate the distribution of lymphocyte subsets and cytokine profiles in HT patients with differences in thyroid function. Peripheral blood was drawn from 18 healthy controls and 54 HT patients (33 patients with mild HT, 21 patients with severe HT). The percentages of B cell subsets, T cell subsets and NK cells were analyzed by flow cytometry...
September 23, 2016: International Immunopharmacology
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