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Lara A Aqrawi, Janicke Liaaen Jensen, Gunnvor Øijordsbakken, Ann-Kristin Ruus, Ståle Nygård, Marit Holden, Roland Jonsson, Hilde Kanli Galtung, Kathrine Skarstein
A characteristic feature of primary Sjögren's syndrome (pSS) is the destruction of salivary and lacrimal glands mediated by mononuclear cell infiltration. Adipocytes can also occupy a large portion of the salivary gland (SG) tissue area, although little is known about their significance in pSS. We have previously investigated adipose tissue infiltration in SG biopsies from pSS patients and non-SS sicca controls. Our findings indicated the distinct incidence of adipose tissue replacement in pSS patients, where adipocytes were detected in interleukin (IL) 6 rich regions...
March 5, 2018: Autoimmunity
Kyosuke Kanai, Ah-Mee Park, Akiko Watanabe, Tomohiro Arikawa, Teruhito Yasui, Hiroki Yoshida, Ikuo Tsunoda, Osamu Yoshie
IL-27 is an immunoregulatory cytokine consisting of p28 and EBI3. Its receptor also has two subunits, WSX1 and gp130. Although IL-27 promotes Th1 differentiation in naive T cells, it also induces IL-10 expression in effector Th1 cells to curtail excessive immune responses. By using p28-deficient mice and WSX1-deficient mice (collectively called IL-27-deficient mice), we examined the role of IL-27 in primary infection by murine γ-herpesvirus 68 (MHV68), a murine model of EBV. Upon airway infection with MHV68, IL-27-deficient mice had more aggravated lung inflammation than wild-type mice, although MHV68 infection per se was better controlled in IL-27-deficient mice...
March 2, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Jianping Hu, Yirong Qin, Shenglan Yi, Chaokui Wang, Jinglu Yang, Lu Yang, Luoziyi Wang, Aize Kijlstra, Peizeng Yang, Hong Li
PURPOSE: Recent studies have reported that IL-35 has a protective effect in autoimmune disease. In this study, we explored the role of IL-35 in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease. METHODS: The IL-35/EBI3 and IL-35/P35 mRNA level was assayed by Real-Time PCR. The level of IL-35 in serum was detected by ELISA. PBMCs and monocyte-derived DCs were cultured with or without IL-35 and the concentration of IL-17, IL-10, IFN-γ, IL-6, TNF-α, and IL-1β in supernatants was tested by ELISA...
March 2, 2018: Ocular Immunology and Inflammation
Jinyan Jiang, Xiangyong Liu
BACKGROUND AND AIM: So far, the understanding of the role of Epstein-Barr virus-induced gene 3 (EBI3) in breast cancer has been limited. This study uncovers the functional role and clinical significance of EBI3 in breast cancer patients. PATIENTS AND METHODS: The expression levels of EBI3, IL-27p28, and IL-12p35 were measured by quantitative real-time reverse transcription (RT)-polymerase chain reaction (PCR). Correlations of EBI3 expression with IL-27p28 and IL-12p35 expression were analyzed using Pearson's correlation assay...
2018: Oncology Research and Treatment
Glen M Scholz, Jacqueline E Heath, Katrina A Walsh, Eric C Reynolds
Interleukin (IL)-36 (IL-36) cytokines are important regulators of mucosal homeostasis and inflammation. We previously established that oral epithelial cells strongly upregulate IL-36γ expression in response to the bacterial pathogen Porphyromonas gingivalis. Here, we have established that IL-36γ stimulates the expression of the IL-12 cytokine family members, IL-23p19 and Epstein-Barr Virus-Induced Gene 3 (EBI3), by oral epithelial cells; their expression was also selectively stimulated by IL-36α. Notably, IL-23p19 and EBI3 expression was not stimulated by P...
February 23, 2018: Immunology and Cell Biology
Tengda Li, Yuanlan Huang, Peng Liu, Yun Liu, Jie Guo, Weiwei Zhang, Mingli Gu, Cheng Qian, Anmei Deng
Primary biliary cirrhosis (PBC) is an autoimmune liver disease. Its histological characteristics, such as progressive intrahepatic bile duct destruction, cholestasis, and liver cirrhosis, are caused by the body's autoimmune disorders. Interleukin (IL)-35 has two subunits (p35 and Ebi3) and is a member of the IL-12 family of heterodimeric cytokines. IL-35 has immunosuppressive functions and plays an important role in many autoimmune diseases. In this study, we compared plasma levels of IL-35 and relative mRNA expression levels of p35 and Ebi3 in peripheral blood mononuclear cells (PBMCs) from 70 PBC patients and 70 healthy individuals...
2018: Tohoku Journal of Experimental Medicine
X Y Song, H Huang, Y Z Liu, S Li, Y Y Zhao, Z J Xu
Objective: To investigate the expression of interleukin(IL)-35 protein and gene in peripheral blood of patients with sarcoidosis and its clinical significance. Methods: Peripheral blood samples from 98 patients with sarcoidosis and 98 healthy volunteers were collected at Peking Union Medical College Hospital between January 2016 and March 2017. The plasma levels of IL-35 were detected by enzyme-linked immunosorbent assays (ELISA), and the relationship between IL-35 and the clinical characteristics was analyzed...
January 12, 2018: Chinese Journal of Tuberculosis and Respiratory Diseases
Maran L Sprouse, Ivan Shevchenko, Marissa A Scavuzzo, Faith Joseph, Thomas Lee, Samuel Blum, Malgorzata Borowiak, Matthew L Bettini, Maria Bettini
Regulatory T cells (Tregs) use a distinct TCR repertoire and are more self-reactive compared with conventional T cells. However, the extent to which TCR affinity regulates the function of self-reactive Tregs is largely unknown. In this study, we used a two-TCR model to assess the role of TCR affinity in Treg function during autoimmunity. We observed that high- and low-affinity Tregs were recruited to the pancreas and contributed to protection from autoimmune diabetes. Interestingly, high-affinity cells preferentially upregulated the TCR-dependent Treg functional mediators IL-10, TIGIT, GITR, and CTLA4, whereas low-affinity cells displayed increased transcripts for Areg and Ebi3 , suggesting distinct functional profiles...
February 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Xiaoqian Wang, Yu Zhang, Zhiding Wang, Xiaoling Liu, Gaizhi Zhu, Gencheng Han, Guojiang Chen, Chunmei Hou, Tianxiao Wang, Beifen Shen, Yan Li, He Xiao, Ning Ma, Renxi Wang
The interleukin (IL)‑12 family cytokines have been examined as therapeutic targets in the treatment of several autoimmune diseases. Our previous study showed that a novel IL‑12 family cytokine, IL‑39 (IL‑23p19/Ebi3) mediates inflammation in lupus‑like mice. In the present study, the effect of anti‑mouse IL‑39 polyclonal antibodies on autoimmune symptoms in lupus‑like mice was investigated. Rabbit anti‑mouse IL‑39 polyclonal antibodies were produced by immunization with recombinant mouse IL‑39, and purified using protein A chromatography...
January 2018: Molecular Medicine Reports
Yang Xi, Niamh M Troy, Denise Anderson, Olga M Pena, Jason P Lynch, Simon Phipps, Anthony Bosco, John W Upham
Though human rhinoviruses (HRVs) are usually innocuous viruses, they can trigger serious consequences in certain individuals, especially in the setting of impaired interferon (IFN) synthesis. Plasmacytoid dendritic cells (pDCs) are key IFN producing cells, though we know little about the role of pDC in HRV-induced immune responses. Herein, we used gene expression microarrays to examine HRV-activated peripheral blood mononuclear cells (PBMCs) from healthy people, in combination with pDC depletion, to assess whether observed gene expression patterns were pDC dependent...
2017: Frontiers in Immunology
Mingqian Li, Judith Eckl, Jan-Michael Abicht, Tanja Mayr, Bruno Reichart, Dolores J Schendel, Heike Pohla
BACKGROUND: Regulatory T cells (Treg) play an important role in maintenance of homeostasis in vivo. Treg application to alleviate allo-organ rejection is being studied extensively. However, natural Treg (nTreg) expansion in vitro is laborious and expensive. Antigen-specific Treg are more effective and require lower cell numbers than use of nTreg for immune control. The baboon, as a non-human primate experimental animal model, is widely used in xenotransplantation research. An effective method to generate baboon xeno-specific Treg would benefit research on immune tolerance in xenotransplantation using this model system...
October 22, 2017: Xenotransplantation
Tiago Silva Medina, Gabriela Gonçalves Oliveira, Maria Cláudia Silva, Bruna Araújo David, Grace Kelly Silva, Denise Morais Fonseca, Renata Sesti-Costa, Amanda Farage Frade, Monique Andrade Baron, Barbara Ianni, Alexandre Costa Pereira, Christophe Chevillard, Edécio Cunha-Neto, José Antonio Marin-Neto, João Santana Silva
The identification of anti-inflammatory mediators can reveal important targetable molecules capable of counterbalancing Trypanosoma cruzi-induced myocarditis. Composed of Ebi3 and IL-27p28 subunits, IL-27 is produced by myeloid cells and is able to suppress inflammation by inducing IL-10-producing Tr1 cells, thus emerging as a potential candidate to ameliorate cardiac inflammation induced by T. cruzi. Although IL-27 has been extensively characterized as a suppressive cytokine that prevents liver immunopathogenesis after T...
2017: Frontiers in Immunology
Chongbiao Huang, Zengxun Li, Na Li, Yang Li, Antao Chang, Tiansuo Zhao, Xiuchao Wang, Hongwei Wang, Song Gao, Shengyu Yang, Jihui Hao, He Ren
BACKGROUND & AIMS: Cells of the monocyte lineage contribute to tumor angiogenesis. Interleukin 35 (IL35) is a member of the IL12 family produced by regulatory, but not effector, T cells. IL35 is a dimer comprising the IL12 alpha and IL27 beta chains, encoded by IL12A and EBI3, respectively. Expression of IL35 is increased in pancreatic ductal adenocarcinomas (PDACs) compared with normal pancreatic tissues, and promotes metastasis. We investigated the role of IL-35 in monocyte-induced angiogenesis of PDAC in mice...
October 5, 2017: Gastroenterology
Ivy M Dambuza, Chang He, Jin Kyeong Choi, Cheng-Rong Yu, Renxi Wang, Mary J Mattapallil, Paul T Wingfield, Rachel R Caspi, Charles E Egwuagu
Interleukin 35 (IL-35) is a heterodimeric cytokine composed of IL-12p35 and Ebi3 subunits. IL-35 suppresses autoimmune diseases while preventing host defense to infection and promoting tumor growth and metastasis by converting resting B and T cells into IL-10-producing and IL-35-producing regulatory B (Breg) and T (Treg) cells. Despite sharing the IL-12p35 subunit, IL-12 (IL-12p35/IL-12p40) promotes inflammatory responses whereas IL-35 (IL-12p35/Ebi3) induces regulatory responses, suggesting that IL-12p35 may have unknown intrinsic immune-regulatory functions regulated by its heterodimeric partner...
September 28, 2017: Nature Communications
Haifei Wang, Jiying Wang, Chao Ning, Xianrui Zheng, Jinlian Fu, Aiguo Wang, Qin Zhang, Jian-Feng Liu
DNA methylation changes play essential roles in regulating the activities of genes involved in immune responses. Understanding of variable DNA methylation linked to immune responses may contribute to identifying biologically promising epigenetic markers for pathogenesis of diseases. Here, we generated genome-wide DNA methylation and transcriptomic profiles of six pairs of polyinosinic-polycytidylic acid-treated pig peripheral blood mononuclear cell (PBMC) samples and corresponding controls using methylated DNA immunoprecipitation sequencing and RNA sequencing...
August 29, 2017: Scientific Reports
Yanfang Liang, Qianqian Chen, Wenjing Du, Can Chen, Feifei Li, Jingying Yang, Jianyu Peng, Dongping Kang, Bihua Lin, Xingxing Chai, Keyuan Zhou, Jincheng Zeng
[This corrects the article DOI: 10.1155/2016/3214105.].
2017: Mediators of Inflammation
Paulina Gorzelak-Pabis, Maciej Chałubiński, Katarzyna Wojdan, Emilia Łuczak, Maciej Borowiec, Marlena Broncel
BACKGROUND: IL-22 is expressed at barrier surfaces, which suggests its critical role in the maintenance of normal barrier homeostasis and tissue repair. IL-22 can both promote pathological inflammation and prevent the destruction of tissues. The functional outcomes of IL-22 on vascular smooth muscle cells, which are shown to regulate immune processes within the vascular wall and which are involved in certain pathologies, have not been analyzed. OBJECTIVES: The effect of IL-22 on the expression of novel antiand pro-inflammatory and barrier disrupting cytokines, apoptosis and the expression of adhesive molecules in human primary aortic smooth muscle cells (AoSMC) was investigated...
May 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Zhihao Liu, Lisha Wu, Jing Zhu, Xiaotong Zhu, Jianmin Zhu, Jin-Qing Liu, Jianchao Zhang, Jonathan P Davis, Sanjay Varikuti, Abhay R Satoskar, Jie Zhou, Ming-Song Li, Xue-Feng Bai
Stem cell antigen-1 (Sca-1/Ly6A/E) is a cell surface glycoprotein that is often used as a biomarker for stem cells and cell stemness. However, it is not clear what factors can directly induce the expression of Sca-1/Ly6A/E in T lymphocytes in vivo, and if induction of Sca-1 is associated with T cell stemness. In this study, we show that interleukin-27 (IL-27), a member of the IL-12 family of cytokines, directly induces Sca-1 expression in T cells in vivo. We found that mice-deficient for IL-27 (either P28 or EBI3) or its signalling (IL-27Rα) had profound reduction of Sca-1 expression in naive (CD62L+  CD44- ), memory (CD62L+  CD44+ ) and effector (CD62L-  CD44+ ) T cells...
December 2017: Immunology
Jacobo Lopez-Abente, Adrián Prieto-Sanchez, Maria-Ángeles Muñoz-Fernandez, Rafael Correa-Rocha, Marjorie Pion
Individuals infected with human immunodeficiency virus type-1 (HIV-1) usually show a general dysregulation and hyper-activation of the immune system. A direct influence of HIV-1 particles on B-cell phenotypes and functions has been previously described. However, the consequences of B-cell dysregulation are still poorly understood. We evaluated the phenotypic changes in primary B cells after direct contact with HIV-1 particles in comparison with different types of stimuli. The functionality of treated B cells was challenged in co-culture experiments with autologous CD4+ and CD8+ T cells...
July 17, 2017: Cellular & Molecular Immunology
Han Ouyang, Li Xiang, Jianchang Chen, Weiting Xu, Yang Jiao, Huaying Shen
INTRODUCTION: Viral myocarditis (VMC) has become an increasingly common heart disease that endangers human health. In the present study, the plasma interleukin-35 (IL-35) level and the percentage of CD4(+)EBI3(+) T cells in VMC patients were detected to investigate the significance of changes in these parameters in the plasma of VMC patients and their association with the disease. MATERIAL AND METHODS: ELISA was performed to detect the plasma IL-35 level and the percentage of peripheral blood CD4(+)EBI3(+) T cells in 40 VMC patients and in 20 healthy individuals...
2017: Central-European Journal of Immunology
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