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Qinghong Wang, Jianguo Liu
IL-27 is a pleiotropic cytokine that has diverse immune regulatory activities under both physiological and pathological conditions. IL-27 enhances the functions of Th1 and CD8(+) T cells, promotes the development of Tfh and Tr1, and suppresses the functions of Th2, Treg, Th9, and Th17 cells. IL-27 is also involved in regulation of immune responses of B cells, NK, DCs, and macrophages. IL-27 production is strictly regulated at both transcriptional and posttranscriptional levels. Given its broad effects on immune regulation, IL-27 has been implicated in the pathogeneses of autoimmune and infectious diseases as well as cancers...
2016: Advances in Experimental Medicine and Biology
Carine Savarin, Cornelia C Bergmann, David R Hinton, Stephen A Stohlman
Viral infections have long been implicated as triggers of autoimmune diseases, including multiple sclerosis (MS), a central nervous system (CNS) inflammatory demyelinating disorder. Epitope spreading, molecular mimicry, cryptic antigen, and bystander activation have been implicated as mechanisms responsible for activating self-reactive (SR) immune cells, ultimately leading to organ-specific autoimmune disease. Taking advantage of coronavirus JHM strain of mouse hepatitis virus (JHMV)-induced demyelination, this study demonstrates that the host also mounts counteractive measures to specifically limit expansion of endogenous SR T cells...
2016: Frontiers in Immunology
Marcela Montes de Oca, Rajiv Kumar, Fabian de Labastida Rivera, Fiona H Amante, Meru Sheel, Rebecca J Faleiro, Patrick T Bunn, Shannon E Best, Lynette Beattie, Susanna S Ng, Chelsea L Edwards, Glen M Boyle, Ric N Price, Nicholas M Anstey, Jessica R Loughland, Julie Burel, Denise L Doolan, Ashraful Haque, James S McCarthy, Christian R Engwerda
The development of immunoregulatory networks is important to prevent disease. However, these same networks allow pathogens to persist and reduce vaccine efficacy. Here, we identify type I interferons (IFNs) as important regulators in developing anti-parasitic immunity in healthy volunteers infected for the first time with Plasmodium falciparum. Type I IFNs suppressed innate immune cell function and parasitic-specific CD4(+) T cell IFNγ production, and they promoted the development of parasitic-specific IL-10-producing Th1 (Tr1) cells...
October 4, 2016: Cell Reports
Guozhen Liu, Jing Luan, Qiang Li
Diffuse large B cell lymphoma (DLBCL) is a common B cell malignancy. Complete remission can be achieved in most patients by conventional treatment with rituximab and chemotherapy. However, a subset of remission individuals will develop a relapsed disease for obscure reasons. CD4(+)Foxp3(-)IL-10(+) cell (Tr1) is a novel cell subtype with the capacity to suppress pro-inflammatory responses, but has not been extensively studied in most tumors. In this study, we investigated the potential role of Tr1 cells in DLBCL...
October 5, 2016: DNA and Cell Biology
Anna Winberg, Olga Nagaeva, Ivan Nagaev, Catarina Lundell, Ignacio Arencibia, Lucia Mincheva-Nilsson, Eva Rönmark, Christina E West
BACKGROUND: There is need for prognostic markers for symptomatic food allergy since current diagnostic methods are insufficient and/or time and labor consuming. OBJECTIVE: To estimate the cytokine mRNA profiles in peripheral blood mononuclear cells (PBMC) before and after a double-blind placebo-controlled food challenge series in schoolchildren with suspected allergy to milk, egg or cod and in healthy controls. Analyses of fecal inflammatory biomarkers before and after the challenge were included...
December 2016: Cytokine
Anna Malgorzata White, David C Wraith
The immune system evolved to respond to foreign invaders and prevent autoimmunity to self-antigens. Several types of regulatory T cells facilitate the latter process. These include a subset of Foxp3(-) CD4(+) T cells able to secrete IL-10 in an antigen-specific manner, type 1 regulatory (Tr1) T cells. Although their suppressive function has been confirmed both in vitro and in vivo, their phenotype remains poorly defined. It has been suggested that the surface markers LAG-3 and CD49b are biomarkers for murine and human Tr1 cells...
2016: Frontiers in Immunology
Zhao Li, Xiaobing Liu, Rongbin Guo, Pengfei Wang
CD4(+)Foxp3(-) type 1 regulatory T (Tr1) cells are potent producers of interleukin 10 (IL-10) and transforming growth factor beta (TGF-β), through which they suppress pathogenic inflammation and autoimmune responses. The role of Tr1 response in glioblastoma multiforme (GBM) is still unclear. Here, we examined the frequency, phenotype, induction mechanism, and function of Tr1 cells in GBM patients. Compared to healthy controls, GBM patients presented significantly higher frequency of Tr1 cells in peripheral blood...
September 16, 2016: International Journal of Biochemistry & Cell Biology
Ruijie Shi, Jiahui Zhang, Jingyuan Li, Ketao Wang, Haiying Jia, Lin Zhang, Putong Wang, Jun Yin, Fanrong Meng, Yongchun Li
DNA methylation is a major epigenetic marker in plants that plays a crucial role in transcriptional and developmental regulation. The DNA methylation 'code' is thought to be 'read' by a set of proteins containing methyl-CpG-binding domain (MBD). However, little is known about MBD genes in common wheat (Triticum aestivum L.). Here, we report the isolation and characterization of TaMBD6 and its homeologues (TaMBD6_A, TaMBD6_B, and TaMBD6_D) in hexaploid wheat. The cDNA was quite different among the three homeologues and InDel mutations were detected in 5'-UTR and coding region...
September 1, 2016: Plant Physiology and Biochemistry: PPB
Tzu-Yu Shao, Ling-Hui Hsu, Chien-Hui Chien, Bor-Luen Chiang
Recent studies have revealed various Foxp3(-) regulatory T (Treg) cell subsets effectively protect mice from colitis. In the present study, we demonstrated that B cells induced a particular subset of regulatory T (Treg-of-B) cells, expressing programmed cell death 1 (PD-1), inducible costimulator (ICOS), lymphocyte-activation gene 3 (LAG3), glucocorticoid-induced tumor necrosis factor receptor (GITR), and OX-40, did not express Foxp3. Treg-of-B cells produced abundant levels of IL-10 and low levels of IL-4 and TGF-β...
2016: Scientific Reports
M A van Leeuwen, L M M Costes, L A van Berkel, Y Simons-Oosterhuis, M F du Pré, A E Kozijn, H C Raatgeep, D J Lindenbergh-Kortleve, N van Rooijen, F Koning, J N Samsom
Celiac disease is caused by inflammatory T-cell responses against the insoluble dietary protein gliadin. We have shown that, in humanized mice, oral tolerance to deamidated chymotrypsin-digested gliadin (CT-TG2-gliadin) is driven by tolerogenic interferon (IFN)-γ- and interleukin (IL)-10-secreting type 1 regulatory T-like cells (Tr1-like cells) generated in the spleen but not in the mesenteric lymph nodes. We aimed to uncover the mechanisms underlying gliadin-specific Tr1-like-cell differentiation and hypothesized that proteolytic gliadin degradation by splenic macrophages is a decisive step in this process...
August 31, 2016: Mucosal Immunology
Rajsmita Bhattacharjee, Dipankar De, Sanjeev Handa, Ranjana W Minz, Biman Saikia, Neha Joshi
BACKGROUND: Robust evidence for the efficacy of rituximab monotherapy in pemphigus is lacking. The effects of rituximab on T-regulatory cells (Tregs) in pemphigus have not been studied. OBJECTIVE: The primary objective was to assess the efficacy of rituximab monotherapy in severe pemphigus vulgaris. The secondary objectives were to assess whether counts of different subsets of Tregs in the peripheral blood correlate with baseline clinical severity and whether clinical response in severe pemphigus is associated with an alteration in the Treg count...
September 1, 2016: Dermatology: International Journal for Clinical and Investigative Dermatology
Mauricio F Farez, Ismael L Calandri, Jorge Correale, Francisco J Quintana
Melatonin is a hormone with complex roles in the pathogenesis of autoimmune disorders. Over the years, it has become clear that melatonin may exacerbate some autoimmune conditions, whereas it alleviates others such as multiple sclerosis. Multiple sclerosis is an autoimmune disorder characterized by a dysregulated immune response directed against the central nervous system. Indeed, the balance between pathogenic CD4(+) T cells secreting IFN-γ (TH 1) or IL-17 (TH 17); and FoxP3(+) regulatory T cells and IL-10(+) type 1 regulatory T cells (Tr1 cells) is thought to play an important role in disease activity...
October 2016: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
Guang-Gang Li, Ying-Hua Cao, Yue Run, Ru-Xiang Xu, Zhen-Dong Zheng
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are caused by rapid-onset bilateral pulmonary inflammation. We therefore investigated the potential role of IL-10(+) CD4(+) Tr1 cells, a regulatory T cell subset with previously identified immunosuppressive functions, in ARDS patients. We first showed that circulating Tr1 cells were upregulated in active and resolved ARDS patients compared to healthy controls and pneumonia patient controls. A significant fraction of these Tr1 cells expressed granzyme B and perforin, while most Tr1 cells did not express interferon gamma (IFN-γ), IL-4, IL-17 or FOXP3, suggesting that the effector functions of these Tr1 cells were primarily mediated by IL-10, granzyme B, and perforin...
August 25, 2016: Clinical and Experimental Pharmacology & Physiology
Ying Ma, Mani Rajkumar, Chang Zhang, Helena Freitas
The aim of this study was to investigate the effects of drought resistant serpentine rhizobacteria on plant growth and metal uptake by Brassica oxyrrhina under drought stress (DS) condition. Two drought resistant serpentine rhizobacterial strains namely Pseudomonas libanensis TR1 and Pseudomonas reactans Ph3R3 were selected based on their ability to stimulate seedling growth in roll towel assay. Further assessment on plant growth promoting (PGP) parameters revealed their ability to produce indole-3-acetic acid, siderophore and 1-aminocyclopropane-1-carboxylate deaminase...
December 15, 2016: Journal of Hazardous Materials
W W Li, P Sun, D D Chen, W Q Wang, G H Jiao, Y J Wang, L Zhou, B M Wang, J Zhang
OBJECTIVE: To investigate the preventive and therapeutic effects of rapamycin (RAPA) on autoimmune hepatitis and liver fibrosis induced by concanavalin A (ConA) and possible mechanisms. METHODS: Female C57BL/6 mice aged 8 weeks were randomly divided into normal control group, ConA model group, and ConA+RAPA treatment group. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured; hematoxylin-eosin and Masson staining and Knodell HAI and Ishak scoring systems were used to evaluate the degrees of liver inflammation and fibrosis...
May 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Xiuhong Piao, Tatsuhiko Ozawa, Hiroshi Hamana, Kiyomi Shitaoka, Aishun Jin, Hiroyuki Kishi, Atsushi Muraguchi
Agonistic tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-receptor-specific antibodies are attractive antitumor therapeutics. Recently, our group has generated several human monoclonal antibodies (mAbs) to TRAIL-receptor-1 (TRAIL-R1) (TR1-IgGs) using ISAAC technology. However, these TR1-IgGs did not demonstrate ideal apoptosis-inducing capacity in the absence of additional antibodies. To overcome this limitation, we class-switched the TR1-IgGs to TRAIL-R1 IgM antibodies (TR1-IgMs); TR1-IgMs might possess high valency and facilitate the crosslinking of the cell surface receptors...
May 2016: Oncoimmunology
K E Rehm, I Sunesara, M T Tull, G D Marshall
Endurance-based exercise training can lead to alterations in components of the immune system, but it is unknown how psychological stress (another potent immunomodulator) may impact these changes. The purpose of this study was to determine the moderating role of psychological stress on exercise-induced immune changes. Twenty-nine recreational runners were recruited for this study four weeks before completing a marathon. Each subject reported: weekly training volume (miles/wk) for the week prior to the study visit; completed the Perceived Stress Scale (PSS), the state version of the State-Trait Anxiety Inventory (STAI) and the Penn State Worry Questionnaire (PSWQ); and donated blood for assessment of CD4+ T cell subpopulations and mitogen-induced cytokine production...
April 2016: Journal of Biological Regulators and Homeostatic Agents
Limei Wang, Zichen Li, Bogoljub Ciric, Farinaz Safavi, Guang-Xian Zhang, Abdolmohamad Rostami
Intravenous (i.v.) injection of a soluble myelin antigen can induce tolerance, which effectively ameliorates experimental autoimmune encephalomyelitis (EAE). We have previously shown that i.v. MOG induces tolerance in EAE and expands a subpopulation of tolerogenic CD11c(+) CD11b(+) dendritic cells (DCs) with an immature phenotype having low expression of IA and co-stimulatory molecules CD40, CD86, and CD80. Here we further investigate the role of tolerogenic DCs in i.v. tolerance by injecting clodronate-loaded liposomes, which selectively deplete CD11c(+) CD11b(+) and immature DCs, but not CD11c(+) CD8(+) DCs and mature DCs...
June 24, 2016: European Journal of Immunology
Dominique Fernández, Felipe Flores-Santibáñez, Jocelyn Neira, Francisco Osorio-Barrios, Gabriela Tejón, Sarah Nuñez, Yessia Hidalgo, Maria Jose Fuenzalida, Daniel Meza, Gonzalo Ureta, Alvaro Lladser, Rodrigo Pacheco, Claudio Acuña-Castillo, Victoria Guixé, Francisco J Quintana, Maria Rosa Bono, Mario Rosemblatt, Daniela Sauma
T helper type 17 (Th17) lymphocytes, characterized by the production of interleukin-17 and other pro-inflammatory cytokines, are present in intestinal lamina propria and have been described as important players driving intestinal inflammation. Recent evidence, supporting the notion of a functional and phenotypic instability of Th17 cells, has shown that Th17 differentiate into type 1 regulatory (Tr1) T cells during the resolution of intestinal inflammation. Moreover, it has been suggested that the expression of CD39 ectonucleotidase endows Th17 cells with immunosuppressive properties...
2016: PloS One
José E Belizário, Wesley Brandão, Cristiano Rossato, Jean Pierre Peron
Our understanding of how thymocytes differentiate into many subtypes has been increased progressively in its complexity. At early life, the thymus provides a suitable microenvironment with specific combination of stromal cells, growth factors, cytokines, and chemokines to induce the bone marrow lymphoid progenitor T-cell precursors into single-positive CD4(+) and CD8(+) T effectors and CD4(+)CD25(+) T-regulatory cells (Tregs). At postthymic compartments, the CD4(+) T-cells acquire distinct phenotypes which include the classical T-helper 1 (Th1), T-helper 2 (Th2), T-helper 9 (Th9), T-helper 17 (Th17), follicular helper T-cell (Tfh), and induced T-regulatory cells (iTregs), such as the regulatory type 1 cells (Tr1) and transforming growth factor-β- (TGF-β-) producing CD4(+) T-cells (Th3)...
2016: Mediators of Inflammation
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