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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 IL35 in monocyte-induced angiogenesis of PDAC in mice...
February 2018: Gastroenterology
Panhong Gou, Xiaoru Chang, Zhonghui Ye, Yueli Yao, Patton Khuu Nguyen, Sally Katharine Hammond, Junling Wang, Sa Liu
Immune system is critical to protecting human health from toxic substances. Our previously published research had found an important link between polycyclic aromatic hydrocarbons (PAHs) in ambient air and changes at the DNA level in immune cells that led to impaired function of regulatory T (Treg) cells in children living in California, USA. But molecular and cellular pathways of these changes remain unclear. The present study aims to explore whether exposure to PAHs leads to changes in Treg cells functions of children living in Gansu, China, where ambient air pollution levels are much higher than those in California, and to explore potential mechanisms of PAH-induced immunological dysfunctions...
October 2017: Environmental Science and Pollution Research International
Fatima Manzoor, Mark C Johnson, Chengwen Li, R Jude Samulski, Bo Wang, Roland Tisch
IL-35 is a recently identified cytokine exhibiting potent immunosuppressive properties. The therapeutic potential and effects of IL-35 on pathogenic T effector cells (Teff) and Foxp3+ Treg, however, are ill defined. We tested the capacity of IL-35 to suppress ongoing autoimmunity in NOD mice. For this purpose, an adeno-associated virus vector in which IL-35 transgene expression is selectively targeted to β cells via an insulin promoter (AAV8mIP-IL35) was used. AAV8mIP-IL35 vaccination of NOD mice at a late preclinical stage of type 1 diabetes (T1D) suppressed β-cell autoimmunity and prevented diabetes onset...
January 2017: European Journal of Immunology
Ilana C van Rensburg, Chandre Wagman, Kim Stanley, Caroline Beltran, Katharina Ronacher, Gerhard Walzl, Andre G Loxton
Activated B-cells increase T-cell behaviour during autoimmune disease and other infections by means of cytokine production and antigen-presentation. Functional studies in experimental autoimmune encephalomyelitis (EAE) indicate that B-cell deficiencies, and a lack of IL10 and IL35 leads to a poor prognosis. We hypothesised that B-cells play a role during tuberculosis. We evaluated B-cell mRNA expression using real-time PCR from healthy community controls, individuals with other lung diseases and newly diagnosed untreated pulmonary TB patients at three different time points (diagnosis, month 2 and 6 of treatment)...
January 10, 2017: Oncotarget
Yusuke Tomita, Miwa Satomi, William Bracamonte-Baran, Ewa Jankowska Gan, Andrea Szymczak Workman, Creg J Workman, Dario Angelo Alberto Vignali, William J Burlingham
BACKGROUND: The influence of donor-side regulation toward recipient antigens on graft outcome is poorly understood. METHODS: Because this influence might be due in part to the accumulation of tissue-resident memory T cells in the donor organ, we used a standard murine tolerization model (donor-specific transfusion plus CD40L blockade) to determine the kinetics of development and peripheralization of allospecific regulatory T cell in lymphoid tissues and liver, a secondary lymphoid organ used in transplantation...
May 2016: Transplantation Direct
S Aggarwal, S N Das
OBJECTIVE: Thiodigalactoside (TDG), a synthetic inhibitor of β-galactoside-binding protein (β-GBP) suppresses tumour growth by inhibiting multiple cancer enhancing activities of β-GBP. Hence, we attempted to understand whether disruption of β-GBP functions and indirect inhibition of Treg cells by TDG affect the growth and establishment of oral cancer cells. METHOD: The growth, morphology, cell cycle regulation, apoptosis induction and angiogenesis of oral cancer cell lines (SCC-4, SCC-9, SCC-25) via MACS-purified Treg cells were performed by MTT, propidium iodide (PI) staining, annexin-V-binding assay and ELISA respectively...
July 2016: Oral Diseases
Yutaka Kurebayashi, Katsura Emoto, Yuichiro Hayashi, Ikuo Kamiyama, Takashi Ohtsuka, Hisao Asamura, Michiie Sakamoto
Neoplastic cancer cells and cancer stroma (including infiltrating immune cells) determine the biology and prognosis of cancer. Various types of adaptive and innate immune cells are known to infiltrate the cancer stroma. However, the patterns and spatial distribution of immune cell infiltration as well as its association with tumor histology remain poorly understood. To address these issues, we comprehensively analyzed the infiltrating immune cells present in lung adenocarcinoma. The principal types of both adaptive and innate infiltrating immune cells were immunohistochemically evaluated in the predominant histologic components of 111 lung adenocarcinomas...
March 2016: Cancer Immunology Research
Adriana Weinberg, Jeong-Gun Park, Ronald Bosch, Alice Cho, Elizabeth Livingston, Fran Aweeka, Yoninah Cramer, D Heather Watts, Amneris E Luque, Susan E Cohn
OBJECTIVES: Depot medroxyprogesterone acetate (DMPA) was associated with increased HIV transmission and accelerated disease progression in untreated women. The potential underlying mechanisms include immune modulation. We evaluated the effect of a single DMPA injection on cell-mediated immunity (CMI), T-cell activation, T-cell regulation (Treg), and inflammation in HIV-infected women on combination antiretroviral regimen (cART). METHODS: Women with HIV plasma RNA ≤ 400 copies per milliliter on stable cART received DMPA and had immunologic and medroxyprogesterone acetate (MPA) measurements at baseline, 4 weeks [peak MPA concentration (Cmax)], and 12 weeks [highest MPA area under the concentration curve]...
February 1, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Charles E Egwuagu, Cheng-Rong Yu
Neuroinflammation contributes to neuronal deficits in neurodegenerative CNS (central nervous system) autoimmune diseases, such as multiple sclerosis and uveitis. The major goal of most treatment modalities for CNS autoimmune diseases is to limit inflammatory responses in the CNS; immune-suppressive drugs are the therapy of choice. However, lifelong immunosuppression increases the occurrence of infections, nephrotoxicity, malignancies, cataractogenesis, and glaucoma, which can greatly impair quality of life for the patient...
2015: Critical Reviews in Immunology
Tiantian Sun, Donglei Zhang, Yanhui Yang, Xian Zhang, Cuicui Lv, Rongfeng Fu, Mingen Lv, Wenjie Liu, Yunfei Chen, Wei Liu, Yueting Huang, Feng Xue, Xiaofan Liu, Lei Zhang, Huiyuan Li, Renchi Yang
Primary immune thrombocytopenia (ITP) is an autoimmune disorder. Interleukin-35 (IL35) can suppress T cell proliferation and elicit the development of inducible regulatory T cells (Tregs). Previous studies have shown decreased plasma IL35 levels and dysfunctional T cells in patients with ITP. In this study, we determined whether decreased IL35 levels correlate with T cell dysfunction in ITP patients. Plasma IL35 levels were found to be lower in ITP patients than in healthy controls, were positively correlated with platelet levels and the percentage of peripheral circulating Tregs, and negatively correlated with the levels of T helper-1 cells in ITP patients...
April 2015: British Journal of Haematology
Yukiko Tone, Yoko Kidani, Chihiro Ogawa, Kouhei Yamamoto, Masato Tsuda, Christian Peter, Herman Waldmann, Masahide Tone
Glucocorticoid-induced TNFR (Gitr) and Ox40, two members of the TNFR superfamily, play important roles in regulating activities of effector and regulatory T cells (Treg). Their gene expression is induced by T cell activation and further upregulated in Foxp3+ Treg. Although the role of Foxp3 as a transcriptional repressor in Treg is well established, the mechanisms underlying Foxp3-mediated transcriptional upregulation remain poorly understood. This transcription factor seems to upregulate expression not only of Gitr and Ox40, but also other genes, including Ctla4, Il35, Cd25, all critical to Treg function...
April 15, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
Juan Ma, Liang-zhi Xie
OBJECTIVE: To express and purify recombinant human interleukin-35[IL-35-IgG1 (Fc) in eukaryotic expression system and to study the interaction of IL-35 with gp130 protein. METHODS: A mammalian expression vector, pSTEP2-IL35-LFc, was constructed and transfected into HEK293T cells. Then rhIL-35-IgG1 (Fc) was expressed and purified with protein A affinity chromatography, and was examined with SDS-PAGE and Western blot analysis. The binding of IL-35 to its receptor gp130 was investigated using enzyme-linked immunosorbent assay (ELISA)...
December 2013: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
Zehra Sema Ozkan, Derya Deveci, Banu Kumbak, Mehmet Simsek, Fulya Ilhan, Samet Sekercioglu, Ekrem Sapmaz
Implantation necessitates complex interactions among the developing embryo, decidualizing endometrium, and developing maternal immune tolerance and/or alterations in cellular and humoral immune responses. Overstimulation of T helper 1 (Th1) or Th2 cytokines in systemic and local environments, alterations of the prevalence of IL17 and regulatory T cell (Treg) cytokines have also been suggested to contribute to the pathogenesis of implantation failure. We aimed to investigate the plasma levels of IL4, IL6, IL10, TNFα, IFNγ, TGFβ, IL17, IL35, and SOCS3 in infertile and fertile women...
June 2014: Journal of Reproductive Immunology
Maria Bettini, Ashley H Castellaw, Greig P Lennon, Amanda R Burton, Dario A A Vignali
Interleukin (IL)-35 is a newly identified inhibitory cytokine used by T regulatory cells to control T cell-driven immune responses. However, the therapeutic potential of native, biologically active IL-35 has not been fully examined. Expression of the heterodimeric IL-35 cytokine was targeted to β-cells via the rat insulin promoter (RIP) II. Autoimmune diabetes, insulitis, and the infiltrating cellular populations were analyzed. Ectopic expression of IL-35 by pancreatic β-cells led to substantial, long-term protection against autoimmune diabetes, despite limited intraislet IL-35 secretion...
June 2012: Diabetes
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