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Mei Song, Xiaojing Ma
Interleukin-35 (IL-35) is the latest addition to the IL-12 family of heterodimeric cytokines, consisting of IL-12 p35 subunit and IL-27β subunit Epstein-Barr virus induced 3 (EBI3). Since its discovery, IL-35 has been shown to exhibit immunosuppressive activities which are distinct from other members of IL-12 family. IL-35 is also unique in that it is expressed primarily by regulatory T-cells (Tregs) rather than by antigen-presenting cells (APCs). IL-35 can directly suppress effector T-cell proliferation and function and inhibit the differentiation of Th17 cells...
2016: Advances in Experimental Medicine and Biology
Motohiko Suzuki, Makoto Yokota, Yoshihisa Nakamura, Shinya Ozaki, Shingo Murakami
BACKGROUND: IL-35 was recently identified as an anti-inflammatory cytokine. We previously reported that recombinant fusion protein of murine IL-35 and human IgG1 Fc fragment (rIL-35) reduced Th2 cytokines (IL-4 and IL-5) in vitro. However, it is unclear whether IL-35 can attenuate nasal allergic responses and symptoms of allergic rhinitis in vivo. METHODS: To investigate the in vivo effect of IL-35 on allergic rhinitis in mice, mice were sensitized with ovalbumin (OVA)...
October 2, 2016: Allergology International: Official Journal of the Japanese Society of Allergology
Linlin Tao, Jie Zhu, Yuefeng Chen, Qinghang Wang, Ying Pan, Qianqian Yu, Birong Zhou, Huaqing Zhu
Interleukin (IL)-35 is an anti-inflammatory cytokine that may have a protective role in atherosclerosis (AS). However, the exact role of IL-35 in the disease, and the etiology of AS, remain incompletely understood. The present study aimed to investigate whether exogenous IL-35 was able to attenuate the formation of atherosclerotic lesions in apoE(-)/(-) mice, and analyze alterations in the expression levels of forkhead box protein 3 (Foxp3) in peripheral blood and the lesions during the progression of AS. ApoE(-)/(-) mice were randomly divided into two groups that received either a basal diet (negative control group) or a high-fat diet (HFD) for 4 weeks...
October 2016: Experimental and Therapeutic Medicine
Shi-Yang Guan, Rui-Xue Leng, Muhammad Imran Khan, Humera Qureshi, Xiang-Pei Li, Dong-Qing Ye, Hai-Feng Pan
Autoimmune diseases contain a large number of pathologies characterized by various factors that contribute to a breakdown in self-tolerance. Cytokine-mediated immunity plays an essential role in the pathogenesis of varieties of autoimmune diseases. Recent studies reveal that interleukin-35 (IL-35), a newly identified cytokine of IL-12 family, is implicated in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), etc. In this review, we will discuss the biological features of IL-35 and summarize recent advances in the role of IL-35 in the development and pathogenesis of autoimmune diseases; the discoveries gained from these findings might translate into future therapies for these diseases...
October 1, 2016: Inflammation
Yanhui Ma, Lei Chen, Guohua Xie, Yunlan Zhou, Chaoyan Yue, Xiangliang Yuan, Yingxia Zheng, Weiwei Wang, Lin Deng, Lisong Shen
IL-35 is a novel heterodimeric and inhibitory cytokine, composed of interleukin-12 subunit alpha (P35) and Epstein-Barr virus -induced gene 3 (EBI3). IL-35 has been reported to be produced by a range of cell types, especially regulatory T cells, and to exert immunosuppressive effects via the STATx signaling pathway. In this study, we demonstrated that IL-35 expression was elevated in both serum and tumors in patients with colorectal cancer. IL-35 mainly expressed in CD4+ T cells in human colorectal cancer tumors and adjacent tissues...
September 22, 2016: Oncotarget
Zhonghua Zhao, Xi Chen, Shengnan Hao, Rui Jia, Nana Wang, Shaoshui Chen, Mianli Li, Chuanxin Wang, Haiting Mao
Interleukin-35 (IL-35) is a recently discovered inhibitory cytokine, which is firstly discovered to be produced by regulatory T cells (Tregs) and proposed as a key effector molecule of Treg function. This study aims to analyze the correlation between IL-35 expression in tumor-infiltrating lymphocytes (TILs) of breast cancer tissue and patients' clinical characteristics. Plasma IL-35 was also determined in 60 patients with breast invasive ductal carcinoma (IDC) and 30 healthy women by enzyme-linked immunosorbent assay...
September 24, 2016: Cytokine
Jasper H Kappen, Stephen R Durham, Hans In 't Veen, Mohamed H Shamji
Clinical and immunologic tolerance are hallmarks of successful allergen immunotherapy (AIT). Clinical benefits such as reduced symptoms, pharmacotherapy intake and improvement of quality of life persist following cessation of treatment. Successful AIT is associated with suppression of allergic inflammatory cells such as mast cells, eosinophils and basophils in target organs. Furthermore, AIT down-regulates type 2 innate lymphoid cells and allergen-specific type 2 T-helper (Th2) cells. The immunologic tolerant state following AIT is associated with the induction of distinct phenotypes of regulatory T-cells (T-regs) including interleukin (IL)-10-, IL-35- and transforming growth factor (TGF)-β- producing T-regs and FoxP3(+) T-regs...
September 27, 2016: Therapeutic Advances in Respiratory Disease
Soheil Tavakolpour, Seyed Moayed Alavian, Shahnaz Sali
BACKGROUND: Identification of effective treatments in hepatitis B virus (HBV) infection remains a controversial topic. Although the currently approved drugs for HBV control the disease's progression and also limit associated outcomes, these drugs may not fully eradicate HBV infection. In addition to better managing patients with chronic hepatitis B (CHB) infection, the induction of seroclearance by these drugs has been a commonly discussed topic in recent years. OBJECTIVES: In this study, we focused on treating CHB infection via the manipulation of T cells' responses to identify possible approaches to cure CHB...
June 2016: Hepatitis Monthly
Wei-Xia Du, Yu He, Hong-Yan Jiang, Qing Ai, Jia-Lin Yu
BACKGROUND: Early onset sepsis (EOS) remains a major cause of morbidity and mortality in newborns; however, current diagnostic tools are inadequate. We evaluated the accuracy of a novel cytokine, interleukin (IL)-35, for the diagnosis of EOS in comparison with other infection markers. METHODS: One hundred fifty-seven neonates with suspected sepsis in the first 3days of life were enrolled in this perspective study. All enrolled patients were divided into infected group and unlikely infected group according to clinical data...
November 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
Willem van de Veen, Barbara Stanic, Oliver F Wirz, Kirstin Jansen, Anna Globinska, Mübeccel Akdis
Immune tolerance to both self-antigens and innocuous non-self-antigens is essential to protect the host against chronic inflammatory diseases and tissue damage. A wide range of cell types and suppressive molecules are involved in induction and maintenance of tolerance. In addition to their key function in the production of immunoglobulins, B cells can regulate immune responses through their surface molecules and secretion of cytokines. Regulatory B (Breg) cells are characterized by their immunosuppressive capacity, which is often mediated through IL-10 secretion...
September 2016: Journal of Allergy and Clinical Immunology
Simon Fillatreau
B lymphocytes provide essential mechanisms of protection against infectious diseases. The secretion of specific antibodies by long-lived plasma cells is thought to account for the improved resistance afforded by most successful vaccines against pathogens. Accordingly, a goal in vaccine development is to induce potent B cell responses in order to drive the efficient formation of long-lived antibody-secreting cells. However, the roles of activated B cells are complex in infectious diseases. It was recently observed that activated B cells could also negatively regulate host defence mechanisms, both during primary infection and, after vaccination, upon secondary challenge, via mechanisms involving their production of the anti-inflammatory cytokines interleukin (IL)-10 and IL-35...
July 2016: Clinical and Experimental Rheumatology
Yuliya Pylayeva-Gupta
Immunosuppressive functions conferred by regulatory cytokines are important for maintaining homeostasis in immune responses. IL35 has recently emerged as a novel regulator of immune responses. Once thought to be specifically expressed by T regulatory cells, induction of IL35 expression has now been detected in multiple cell types in a variety of diseases, prompting research into regulation of its expression, signaling specificity, target cell populations, and functional outputs. Recent studies have revealed that by directing de novo generation of regulatory T and B cells and inhibiting T effector responses, IL35 plays an important role in the development of autoimmune diseases and cancer...
October 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Hakki Yilmaz, M Cakmak, B Ceydilek, C Demir, A Aktas
OBJECTIVE: Interleukin-35 (IL-35), an interleukin-12 (IL-12) cytokine family member, is shown to be a potent immunosuppressive and anti-inflammatory cytokine. Inducible regulatory T cells (Tregs) produce IL-35 that mediates the immune inhibitory function of Tregs. Growing evidence revealed that upregulation of IL-35 expression may play a critical role in the prevention of autoimmune diseases in various experimental autoimmunity models and vice versa. Hashimoto's thyroiditis (HT) is considered to be a Treg cell-related autoimmune disease with loss of self-tolerance...
April 2016: Endocrine Regulations
Ai Yan, Hui You, Xuedong Zhang
PURPOSE: To examine the role of interleukin 27(IL-27) and interleukin 35 (IL-35) in diabetic retinopathy (DR). METHODS: Patients with diabetes mellitus were divided into three groups: diabetes without retinopathy (DWR), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). Patients with idiopathic macular epiretinal membrane (IMEM) were included as a control group. The serum and vitreous levels of IL-27 and IL-35 were measured using ELISA...
August 18, 2016: Ocular Immunology and Inflammation
Junfeng Zhang, Yi Lin, Chunlei Li, Xiaomei Zhang, Lin Cheng, Lei Dai, Youcui Wang, Fangfang Wang, Gang Shi, Yiming Li, Qianmei Yang, Xueliang Cui, Yi Liu, Huiling Wang, Shuang Zhang, Yang Yang, Rong Xiang, Jiong Li, Dechao Yu, Yuquan Wei, Hongxin Deng
IL-35 downregulates Th17 cell development and suppresses certain types of autoimmune inflammation such as collagen-induced arthritis and experimental autoimmune uveitis. Psoriasis is thought to be initiated by abnormal interactions between cutaneous keratinocytes and systemic immune cells. However, the role of IL-35 in psoriasis remains unclear. In this study, we assessed IL-35 in three well-known psoriasis models: a human keratinocyte cell line (HaCaT), a keratin 14 (K14)-vascular endothelial growth factor A (VEGF-A)-transgenic (Tg) mouse model, and an imiquimod-induced psoriasis mouse model...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Liguo Yin, Yongpeng Ge, Hanbo Yang, Qinglin Peng, Xin Lu, Yamei Zhang, Guochun Wang
The objectives of this study are to assess the levels of serum Interleukin-35 (IL-35) in patients with idiopathic inflammatory myopathies (IIMs) and to evaluate the association between IL-35 levels and IIM-related features. Serum IL-35 was detected in 76 patients with dermatomyositis (DM), 28 patients with polymyositis (PM), 98 disease controls (40 rheumatoid arthritis (RA), 34 systemic lupus erythematosus (SLE), 12 systemic sclerosis (SSc), and 12 sjogren syndrome (SS)), and 43 healthy controls by ELISA. Follow-up was conducted on 34 patients...
November 2016: Clinical Rheumatology
Sabine Ringkowski, Joshua Loke, Shuying Huang, Hasib Ahmadzai, Felix J F Herth, Paul S Thomas, Cristan Herbert
RATIONALE: Granulomas in sarcoidosis have recently been described as containing Interleukin (IL)-27, one of the members of the IL-12 family of cytokines, which also includes IL-35. Levels of these cytokines and the IL-27 receptor subunits were hypothesised to differ between patients with sarcoidosis compared to healthy controls in peripheral blood. METHODS: Using a cross-sectional study design, plasma and peripheral blood mononuclear cells (PBMC) were collected from patients and control subjects...
August 2016: Respiratory Medicine
Chao Hou, Qianni Wu, Chen Ouyang, Ting Huang
In order to explore the potential effects of interleukin (IL)-35 on IL-10, transforming growth factor-β (TGF-β), interferon-γ (INF)-γ, IL-12 and IL-17, a pcDNA3.1‑IL-35 plasmid was injected into the vitreous cavity of BALB/c mice. Enzyme-linked immunosorbent assay, western blot analysis and quantitative PCR analysis were performed to confirm the successful expression of IL-35. Slit-lamp biomicroscopy, hematoxylin and eosin staining and immunofluorescence were employed to detect the status of eyes, and western blot analysis was performed to examine the expression of corneal graft rejection-related cytokines...
September 2016: International Journal of Molecular Medicine
H Ch Li, Y X Zhang, Y Liu, Q Sh Wang
We investigated the effect of the IL-17 monoclonal antibody Secukinumab combined with IL-35 in the blockade of the Notch signaling pathway on the invasive capability of hepatoma cells. We examined the effects of IL-17 antibody or IL-35 treatment alone or in combination on cell invasion and migration capabilities with Transwell chambers. The mRNA levels of Hes1, Hes5, and Hey1 were tested using quantitative polymerase chain reaction. The protein expression of N1ICD, Snail, and E-cadherin protein expressions were measured with western blot...
2016: Genetics and Molecular Research: GMR
Madhura Modak, Otto Majdic, Petra Cejka, Sabrina Jutz, Alexander Puck, Jens G Gerwien, Peter Steinberger, Gerhard J Zlabinger, Herbert Strobl, Johannes Stöckl
Co-receptors, being either co-stimulatory or co-inhibitory, play a pivotal role in T cell immunity. Several studies have indicated that CD43, one of the abundant T cell surface glycoproteins, acts not only as a potent co-receptor but also as a negative regulator for T cell activation. Here we demonstrate that co-stimulation of human peripheral blood T cell via two distinct CD43 epitopes recognized by mAbs CD43-6E5 (T6E5-act ) and CD43-10G7 (T10G7-act ) potently induced T cell proliferation. However, T cell co-stimulation via two CD43 epitopes differentially regulated activation of NFAT and NF-κB transcription factors, T cell cytokine production and effector function...
July 8, 2016: Immunology
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