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Seung-Chul Choi, Zhiwei Xu, Wei Li, Hong Yang, Derry C Roopenian, Herbert C Morse, Laurence Morel
Mouse models of lupus have shown that multiple immune cell types contribute to autoimmune disease. This study sought to investigate the involvement of B cells and dendritic cells in supporting the expansion of inflammatory and regulatory CD4+ T cells that are critical for lupus pathogenesis. We used lupus-prone B6.NZM2410.Sle1.Sle2.Sle3 (TC) and congenic C57BL/6J (B6) control mice to investigate how the genetic predisposition of these two cell types controls the activity of normal B6 T cells. Using an allogeneic in vitro assay, we showed that TC B1-a and conventional B cells expanded Th17 cells significantly more than their B6 counterparts...
March 21, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Z H Lin, H Liu, L Zhu, X Yang, Y P Zhang, J Qian, H Y Liu
Objective: To explore the effects and possible mechanism of rapamycin (RAPA) on apoptosis of CD4+ CD25+ Tregs from the mouse severe aplastic anemia (SAA) model. Methods: The BALB/c female SAA model mice were induced by interferon-gamma in combination with busulphan. The SAA model mice were intraperitoneal injection with RAPA at daily dose of 0.5 mg/kg for 5 days (the RAPA-treated group, n =15) in the SAA group ( n =15) and the un-treated group ( n =15) were control. Bone marrow hematopoiesis changes were observed by the patho-morphological examination of femurs...
March 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Mads N Olesen, Josefine R Christiansen, Steen Vang Petersen, Poul Henning Jensen, Wojciech Paslawski, Marina Romero-Ramos, Vanesa Sanchez-Guajardo
We have previously shown that immunological processes in the brain during α-synuclein-induced neurodegeneration vary depending on the presence or absence of cell death. This suggests that the immune system is able to react differently to the different stages of α-synuclein pathology. However, it was unclear whether these immune changes were governed by brain processes or by a direct immune response to α-synuclein modifications. We have herein locally increased the peripheral concentration of α-synuclein or its pathology-associated variants, nitrated or fibrillar, to characterize the modulation of the CD4 T cell pool by α-synuclein and brain microglia in the absence of any α-synuclein brain pathology...
January 2018: Heliyon
Crystal A Shanley, Marcela I Henao-Tamayo, Chand Bipin, Raja Mugasimangalam, Deepshika Verma, Diane J Ordway, Elizabeth M Streicher, Ian M Orme
Transmission of Mycobacterium tuberculosis bacilli from one individual to another is the basis of the disease process. While considerable emphasis has been placed on the role of host mechanisms of resistance in establishing or preventing new infection, far less has been expended on understanding possible factors operative at the bacterial level. In this study we established a panel of clinical isolates of M. tuberculosis strains obtained from the Western Cape region of South Africa, each of which had been carefully tracked in terms of their degree of transmission in the community...
March 2018: Tuberculosis
Baoren Zhang, Yi Liu, Xu Lan, Xiaoxi Xu, Xiaoning Zhang, Xiang Li, Yiming Zhao, Guang Li, Caigan Du, Shanzheng Lu, Hao Wang
BACKGROUND: Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) characterized by chronic inflammation of colon. It is commonly believed that the imbalance of immune system and overwhelming production of cytokines are involved in the pathogenesis of UC. Recent studies demonstrated that interleukin-35 (IL-35), a key player in the regulation of inflammation, has been identified as potential therapeutic target to treat UC. However, conventional intravenous administration is costly and inconvenient...
March 20, 2018: Journal of Translational Medicine
Linlin Dong, Xiaoyu Zheng, Kun Wang, Guonian Wang, Huichao Zou
BACKGROUND: The T-helper 17 (Th17)/regulatory T (Treg) balance is essential for immune homeostasis. But the effects of gastric surgery on this balance remain unclear. The aim of present study is to identify the influence of gastric surgery on Th17/Treg balance and the role of programmed death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway in this process. METHODS: Mice were divided into Control, Sham and Surgery group randomly. Animals in Surgery group accepted partial gastrectomy...
March 16, 2018: Journal of Trauma and Acute Care Surgery
Shimpei Kawamoto
No abstract text is available yet for this article.
2018: Arerugī, [Allergy]
Tomotaka Kawayama, Takashi Kinoshita, Kazuko Matsunaga, Yoshiko Naito, Jun Sasaki, Yoshikazu Tominaga, Tomoaki Hoshino
Asthma is an allergic disease characterized by chronic airway inflammation, airway hyperresponsiveness (AHR), reversibility and remodeling. Inhaled corticosteroids (ICS) are effective in many patients with asthma. However, ICS are a controlling, but not but curative treatment, and there are still many patients with refractory and difficult-to-treat asthma. The evaluation of airway inflammation by induced sputum, non-specific AHR by methacholine, and asthmatic reactions by specific allergen challenge techniques are useful not only to investigate the pathogenesis of asthma but also to help develop new drugs for asthma management...
March 16, 2018: Kurume Medical Journal
Henrieta Fraser, Niloufar Safinia, Nathali Grageda, Sarah Thirkell, Katie Lowe, Laura J Fry, Cristiano Scottá, Andrew Hope, Christopher Fisher, Rachel Hilton, David Game, Paul Harden, Andrew Bushell, Kathryn Wood, Robert I Lechler, Giovanna Lombardi
The concept of regulatory T cell (Treg)-based immunotherapy has enormous potential for facilitating tolerance in autoimmunity and transplantation. Clinical translation of Treg cell therapy requires production processes that satisfy the rigors of Good Manufacturing Practice (GMP) standards. In this regard, we report our findings on the implementation of a robust GMP compliant process for the ex vivo expansion of clinical grade Tregs, demonstrating the feasibility of this developed process for the manufacture of a final product for clinical application...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
Zilong Hu, Shidong Hu, Youjun Wu, Songyan Li, Changzheng He, Xiaowei Xing, Yufeng Wang, Xiaohui Du
Although adoptive cell therapy (ACT) has demonstrated effective and remarkable clinical responses in several studies, this approach does not lead to objective clinical responses in all cases. The function of ACT is often compromised by various tumor escape mechanisms, including the accumulation of immunoregulatory cells. As a result of peritoneal metastasis in the terminal stage, malignant ascites fluid lacks effectiveness and is a poor prognostic factor for gastric cancer. The present study assessed T-cell subsets in lymphocytes derived from malignant ascites, and investigated the effects of arsenic trioxide (As2 O3 ) on regulatory T cells (Tregs) and ascites-derived tumor-infiltrating lymphocytes (TILs) in vitro ...
April 2018: Oncology Letters
Yueming Shen, Yuanhong Xie, Yan Zhao, Yan Long, Lingqian Li, Ya Zeng
Pim-1 kinase has been implicated in inflammatory bowel disease (IBD). This study aimed to evaluate the application of Pim-1 inhibitor (PIM-Inh) for the treatment of IBD. Mouse model of IBD was established by the treatment with trinitrobenzene sulphonic acid (TNBS). The results showed that disease activity index score was significantly decreased, colon length was significantly increased while Wallace score and pathological score were significantly decreased after PIM-Inh treatment compared to TNBS model group...
March 15, 2018: Clinics and Research in Hepatology and Gastroenterology
Zhi-Wei Lai, Ryan Kelly, Thomas Winans, Ivan Marchena, Ashwini Shadakshari, Julie Yu, Maha Dawood, Ricardo Garcia, Hajra Tily, Lisa Francis, Stephen V Faraone, Paul E Phillips, Andras Perl
BACKGROUND: Patients with systemic lupus erythematosus have T-cell dysfunction that has been attributed to the activation of the mammalian target of rapamycin (mTOR). Rapamycin inhibits antigen-induced T-cell proliferation and has been developed as a medication under the generic designation of sirolimus. We assessed safety, tolerance, and efficacy of sirolimus in a prospective, biomarker-driven, open-label clinical trial. METHODS: We did a single-arm, open-label, phase 1/2 trial of sirolimus in patients with active systemic lupus erythematosus disease unresponsive to, or intolerant of, conventional medications at the State University of New York Upstate Medical University (Syracuse, NY, USA)...
March 15, 2018: Lancet
Li-Mei Qu, Shu-Hua Wang, Kun Yang, David R Brigstock, Li Sun, Run-Ping Gao
BACKGROUND: The diagnosis of drug-induced autoimmune hepatitis (DIAIH) and its differentiation from idiopathic autoimmune hepatitis (AIH) is challenging. This study aimed to differentiate DIAIH from AIH by comparing the biochemical changes, histological features, and frequencies of CD4+ Foxp3+ CD25+/- regulatory T cells (Tregs) in liver tissues or peripheral blood lymphocytes. METHODS: A total of 15 DIAIH patients and 24 AIH patients who underwent liver biopsies at initial presentation were enrolled in this study...
February 19, 2018: Hepatobiliary & Pancreatic Diseases International: HBPD INT
S N Yang, X Pu, S L Xiang, J P Chen, L Pei
Objective: To investigate the effect of brain derived neurotrophic factor (BDNF) on mesenchymal stem cells (MSC) inhibiting follicular helper T cells (Tfh cells). Methods: The contents of indoleamine 2,3-dioxygenase (IDO), IL-10, TGF-β and IL-21 in MSC culture supernatant were detected by ELISA; The peripheral blood of healthy volunteers were collected, and lymphocyte in peripheral blood was separated by human lymphocyte separation solution; Co-cultures of MSC and lymphocyte were performed by Transwell chamber, and the proportion of CD4(+)CXCR5(+) Tfh cells and their subtypes were detected by flow cytometry...
January 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
K M Okoniewska, A E Kedzierska, J Okoniewski, A Slawek, K Grzymajlo, A Chelmonska-Soyta, T Grabowski
Epitopes of regulatory T cells (tregitopes) represent linear sequences of amino acids that induce CD4+ CD25+ Foxp3+ T lymphocytes expansion both in vitro and in vivo. The tregitopes' effectiveness was confirmed in autoimmune disease mouse models and in murine transplant models. Therefore, tregitopes together with regulatory T cells (Tregs) could play a major role in maintaining immune tolerance. The purpose of the presented study was a selection of potential tregitopes and assessment of their impact on Tregs expansion...
December 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Yuan Gao, Xiaoju Li, Zhen Shu, Kuo Zhang, Xiaochang Xue, Weina Li, Qiang Hao, Zhaowei Wang, Wangqian Zhang, Shuning Wang, Cheng Zeng, Dong Fan, Wei Zhang, Yingqi Zhang, Huadong Zhao, Meng Li, Cun Zhang
FOXP3 is an important X-linked suppressor of breast cancer. It is reported that FOXP3 is usually mutant, absent, or cytoplasmic distribution in breast cancer cells, which increases the risk of breast cancer. However, in our study the full-length FOXP3 transcript can be detected in breast cancer cells and nuclear FOXP3 is expressed in some breast cancer samples. Therefore, an important question is how the tumor-suppressive function of wild-type FOXP3 is negated in these cancers. We found that Gal-1 is a novel interacting protein of FOXP3 in breast cancer...
March 16, 2018: Cell Death & Disease
Andrea Mencarelli, Hanif Javanmard Khameneh, Jan Fric, Maurizio Vacca, Sary El Daker, Baptiste Janela, Jing Ping Tang, Sabrina Nabti, Akhila Balachander, Tong Seng Lim, Florent Ginhoux, Paola Ricciardi-Castagnoli, Alessandra Mortellaro
The intestinal immune system can respond to invading pathogens yet maintain immune tolerance to self-antigens and microbiota. Myeloid cells are central to these processes, but the signaling pathways that underlie tolerance versus inflammation are unclear. Here we show that mice lacking Calcineurin B in CD11chigh MHCII+ cells (Cnb1CD11c mice) spontaneously develop intestinal inflammation and are susceptible to induced colitis. In these mice, colitis is associated with expansion of T helper type 1 (Th1) and Th17 cell populations and a decrease in the number of FoxP3+ regulatory T (Treg) cells, and the pathology is linked to the inability of intestinal Cnb1-deficient CD11chigh MHCII+ cells to express IL-2...
March 16, 2018: Nature Communications
Yulin Chen, Jie Wu, Jiajia Wang, Wenjing Zhang, Bohui Xu, Xiaojun Xu, Li Zong
AIMS/HYPOTHESIS: The intestinal immune system is an ideal target to induce immune tolerance physiologically. However, the efficiency of oral protein antigen delivery is limited by degradation of the antigen in the gastrointestinal tract and poor uptake by antigen-presenting cells. Gut dendritic cells (DCs) are professional antigen-presenting cells that are prone to inducing antigen-specific immune tolerance. In this study, we delivered the antigen heat shock protein 65-6×P277 (H6P) directly to the gut DCs of NOD mice through oral vaccination with H6P-loaded targeting nanoparticles (NPs), and investigated the ability of this antigen to induce immune tolerance to prevent autoimmune diabetes in NOD mice...
March 15, 2018: Diabetologia
Zhaodong Li, Ludovica F Buttó, Kristine-Anne Buela, Li-Guo Jia, Minh Lam, John D Ward, Theresa T Pizarro, Fabio Cominelli
Death receptor 3 (DR3), a member of the tumor necrosis factor receptor (TNFR) superfamily, has been implicated in regulating T-helper type-1 (TH 1), type-2 (TH 2), and type-17 (TH 17) responses as well as regulatory T cell (Treg ) and innate lymphoid cell (ILC) functions during immune-mediated diseases. However, the role of DR3 in controlling lymphocyte functions in inflammatory bowel disease (IBD) is not fully understood. Recent studies have shown that activation of DR3 signaling modulates Treg expansion suggesting that stimulation of DR3 represents a potential therapeutic target in human inflammatory diseases, including Crohn's disease (CD)...
2018: Frontiers in Immunology
Dalia E Gaddis, Lindsey E Padgett, Runpei Wu, Chantel McSkimming, Veronica Romines, Angela M Taylor, Coleen A McNamara, Mitchell Kronenberg, Shane Crotty, Michael J Thomas, Mary G Sorci-Thomas, Catherine C Hedrick
Regulatory T (Treg) cells contribute to the anti-inflammatory response during atherogenesis. Here we show that during atherogenesis Treg cells lose Foxp3 expression and their immunosuppressive function, leading to the conversion of a fraction of these cells into T follicular helper (Tfh) cells. We show that Tfh cells are pro-atherogenic and that their depletion reduces atherosclerosis. Mechanistically, the conversion of Treg cells to Tfh cells correlates with reduced expression of IL-2Rα and pSTAT5 levels and increased expression of IL-6Rα...
March 15, 2018: Nature Communications
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