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Marlen Vitales-Noyola, Rita Martínez-Martínez, Juan P Loyola-Rodríguez, Lourdes Baranda, Perla Niño-Moreno, Roberto González-Amaro
BACKGROUND: Periodontal disease is chronic inflammatory process that affects the attachment structures of the teeth and constitutes a significant cause of tooth loss in adults. Although different bacteria play an important role in the triggering of this condition, the progression and severity of the disease are strongly affected by the host immune response, which is under the control of different immune-regulatory mechanisms, including T regulatory (Treg) cells. The aim of this study was to assess the frequency and function of CD69(+) Treg lymphocytes in patients with chronic periodontal disease...
October 19, 2016: Journal of Oral Pathology & Medicine
Rikki A Cannioto, Lara E Sucheston-Campbell, Shalaka Hampras, Ellen L Goode, Keith Knutson, Roberta Ness, Francesmary Modugno, Paul K Wallace, J Brian Szender, Paul Mayor, Chi-Chen Hong, Janine M Joseph, Grace Friel, Warren Davis, Mary Nesline, Kevin H Eng, Robert P Edwards, Bridget Kruszka, Kristina Schmitt, Kunle Odunsi, Kirsten B Moysich
OBJECTIVE: There is a mounting body of evidence demonstrating higher percentages of regulatory T (Treg) cells in the peripheral blood of patients with cancer in comparison to healthy controls, but there is a paucity of epidemiological literature characterizing circulating Treg cells among patients with epithelial ovarian cancer (EOC). To investigate the role of peripheral Treg cells in ovarian neoplasms, we conducted a case-control study to characterize circulating concentrations of Treg cells among patients with EOC, women with benign ovarian conditions, and healthy controls without a history of cancer...
October 18, 2016: International Journal of Gynecological Cancer
Qingsheng Li, Nejat K Egilmez
The critical contribution of CD4+CD25+Foxp3+ T-regulatory cells (Treg) to immune suppression in the tumor microenvironment is well-established. Whereas the mechanisms that drive the generation and accumulation of Treg in tumors have been an active area of study, the information on their origin and population dynamics remains limited. In this review, we discuss the ontogeny of tumor-associated Treg in light of the recently identified lineage markers.
October 19, 2016: Immunological Investigations
Behjatolah Monzavi-Karbassi, Fariba Jousheghany, Thomas Kieber-Emmons
Development of cancer vaccines targeting tumor-associated antigens (TAAs) is an alternative approach to chemotherapy with sustained anti-tumor effects. The success of active immunotherapy has been hampered by tumor-induced immune suppressors. Regulatory T cells (Tregs) are a population of immune suppressors with a proven role in regulating anti-tumor immune responses. Removing or subduing Tregs activity leads to more robust anti-tumor immune responses. Here, we used a cell-based vaccination strategy in the 4T1 murine mammary model to examine whether bulk removal of certain TAAs, using their glycan profile, can affect the immunogenicity of the vaccine...
October 19, 2016: Immunological Investigations
Paula D Bos
A prerequisite for tumor evolution toward a malignant state is the establishment of cell intrinsic and extrinsic mechanisms of immune suppression (Hanahan and Weinberg, 2000, 2011; Schreiber, Old, and Smyth, 2011). Widespread recruitment of Foxp3(+) regulatory T cells (TREG) is a prevailing means to dampen antitumor immunity. Advances in the characterization of TREG cell heterogeneity and physiological function of tissue resident TREG cells unfold new possibilities for nontraditional tumor-promoting functions of intratumoral TREG cells...
October 19, 2016: Immunological Investigations
Katarzyna Sznurkowska, Anton Żawrocki, Jacek Sznurkowski, Maciej Zieliński, Piotr Landowski, Katarzyna Plata-Nazar, Ewa Iżycka-Świeszewska, Piotr Trzonkowski, Agnieszka Szlagatys-Sidorkiewicz, Barbara Kamińska
BACKGROUND/AIMS: To determine the proportion of T-regulatory cells (CD4(+)CD25(high)FOXP3(+) cells) in peripheral blood and the number of FOXP3(+) cells in intestinal mucosa of children with inflammatory bowel disease (IBD), and to verify whether these parameters correlate with the activity of the disease. MATERIAL AND METHODS: 24 patients newly diagnosed for IBD were included in the study: ulcerative colitis (UC; n = 13) and Crohn's disease (CD; n = 11). Seventeen healthy controls (HC) and 16 patients with irritable bowel syndrome (IBS) served as a control group for peripheral and intestinal Tregs assessment, respectively...
October 19, 2016: Immunological Investigations
Jun P Ren, Lin Wang, Juan Zhao, Ling Wang, Shun B Ning, Mohamed El Gazzar, Jonathan P Moorman, Zhi Q Yao
Myeloid-derived suppressor cells (MDSCs) and microRNAs (miRNAs) contribute to attenuating immune responses during chronic viral infection; however, the precise mechanisms underlying their suppressive activities remain incompletely understood. We have recently shown marked expansion of MDSCs that promote regulatory T (Treg) cell development in patients with chronic hepatitis C virus (HCV) infection. Here we further investigated whether the HCV-induced expansion of MDSCs and Tregs is regulated by a miRNA-mediated mechanism...
October 18, 2016: Immunology
Jan Klocke, Katharina Kopetschke, Anna-Sophie Grießbach, Valerie Langhans, Jens Y Humrich, Robert Biesen, Duska Dragun, Andreas Radbruch, Gerd-Rüdiger Burmester, Gabriela Riemekasten, Philipp Enghard
Renal infiltration of inflammatory cells contributes to the pathogenesis of Lupus nephritis (LN). Current knowledge on the recruitment mechanisms relies mainly on findings in rodent models. Here, we assess various chemokine pathways in human LN by comparing urinary chemokine concentrations (in 25 patients with acute LN and in 78 lupus patients without active LN) with the expression of corresponding chemokine receptors on urinary leukocytes (in ten acute LN patients). Nine urinary chemokines were significantly elevated in LN patients and correlated with renal disease activity and urinary cell counts; however, their concentrations displayed considerable interindividual heterogeneity...
October 18, 2016: European Journal of Immunology
Xiao-Wen Zhu, Hai-Zhen Zhu, You-Qing Zhu, Mao-Hui Feng, Jian Qi, Zhi-Fen Chen
The mechanism underlying CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) promoting the development of colorectal cancer (CRC) was elucidated in the present study. Forty-eight cases of colorectal carcinomas, 22 cases of colon polyps and 21 cases of normal colorectal tissues were collected. The correlation among Foxp3, IL-10 and Stat3, and the clinical relevance of these three indexes were analyzed. The results showed that the levels of Foxp3 expressed in infiltrating CD4(+)CD25(+)Foxp3(+)Tregs, and IL-10 and Stat3 in CRC tissues were all significantly higher than those in polypus tissues and normal colon tissues (P< 0...
October 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
Samuel Torres-Landa, Janette Furuzawa-Carballeda, Enrique Coss-Adame, Miguel A Valdovinos, Edgar Alejandro-Medrano, Bárbara Ramos-Ávalos, Braulio Martínez-Benítez, Gonzalo Torres-Villalobos
The aim of the study was to characterize the presence of diverse CD4 and CD8 T cell subsets and regulatory cells in peripheral blood and lower oesophageal sphincter (LES) from a young patient with BE/achalasia without treatment versus achalasia group. In order to characterize the circulating cells in this patient, a cytometric analysis was performed. LES tissue was evaluated by double-immunostaining procedure. Five healthy blood donors, 5 type achalasia patients, and 5 oesophagus tissue samples (gastrooesophageal junction) from transplant donors were included as control groups...
2016: Case Reports in Gastrointestinal Medicine
Hyun Sook Hong, Dae Yeon Hwang, Ju Hyeong Park, Suna Kim, Eun Jung Seo, Youngsook Son
Intestinal inflammation alters immune responses in the mucosa and destroys colon architecture, leading to serious diseases such as inflammatory bowel disease (IBD). Thus, regulation of inflammation is regarded as the ultimate therapy for intestinal disease. Substance-P (SP) is known to mediate proliferation, migration, and cellular senescence in a variety of cells. SP was found to mobilize stem cells from bone marrow to the site of injury and to suppress inflammatory responses by inducing regulatory T cells (Tregs) and M2 macrophages...
October 14, 2016: Cytokine
Xiao-Yan Cai, Xiao-Chun Ni, Yong Yi, Hong-Wei He, Jia-Xing Wang, Yi-Peng Fu, Jian Sun, Jian Zhou, Yun-Feng Cheng, Jian-Jun Jin, Jia Fan, Shuang-Jian Qiu
Nucleoside triphosphate diphosphohydrolase-1 (ENTPD1/CD39) is the rate-limiting enzyme in a cascade leading to the generation of immunosuppressive adenosine and plays an important role in tumor progression. This study aimed to evaluate the expression of CD39 and CD39Foxp3 regulatory T cells (Tregs) and to determine their prognostic role in patients with hepatocellular carcinoma (HCC) after radical resection.Immunohistochemistry (IHC) and double IHC were used to analyze CD39 expression or the expression of CD39 and Foxp3 in a cohort of 324 HCC patients who underwent curative resection...
October 2016: Medicine (Baltimore)
Qinyi Zhu, Xiaoli Wu, Yueqian Wu, Xipeng Wang
Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. Inflammatory cells in the EOC microenvironment play a key role in tumor progression. In the present study, we investigated the mechanism of the accumulation of regulatory T cells (Tregs) induced by interleukin-10 (IL-10) derived from tumor-associated macrophages (TAMs) in the EOC microenvironment. The frequency of Tregs and TAMs was detected by immunofluorescence in 40 EOC tissues and 20 benign ovarian tumors, as well as the expression of IL-10 which was assessed by immunohistochemistry...
September 28, 2016: Oncology Reports
Martina Gatzka
Tumor necrosis factor alpha (TNF-α) and Interleukin 17 (IL-17) are key cytokines driving psoriasis and other inflammatory autoimmune diseases and thus represent effective targets for anti-psoriatic therapy. In a recent issue of The Journal of Pathology, Leite Dantas et al. explore a mouse model of TNF-mediated psoriasiform dermatitis and arthritis with Doxycyclin-inducible general over-expression of human TNF (ihTNFtg mice) for the contributions of macrophages and T cells in skin inflammation - with some unexpected and interesting findings...
October 17, 2016: Journal of Pathology
Lijun Fang, Huaijun Tu, Wei Guo, Shixuan Wang, Ting Xue, Fei Yang, Xiaoyan Zhang, Yazhi Yang, Qian Wan, Zhexin Shi, Xulong Zhan, Jian Li
The TSC1/2 heterodimer, a key upstream regulator of the mTOR, can inhibit the activation of mTOR, which plays a critical role in immune responses after bacterial infections. Monocytes are an innate immune cell type that have been shown to be involved in bacteremia. However, how the mTOR pathway is involved in the regulation of monocytes is largely unknown. In our study, TSC1 KO mice and WT mice were infected with E. coli. When compared to WT mice, we found higher mortality, greater numbers of bacteria, decreased expression of coactivators in monocytes, increased numbers of Tregs, and decreased numbers of effector T cells in TSC1 KO mice...
2016: Mediators of Inflammation
Chantal Kuhn, Rafael M Rezende, Andre Pires da Cunha, Fabrice Valette, Francisco J Quintana, Lucienne Chatenoud, Howard L Weiner
CD3-specific monoclonal antibody (mAb) treats autoimmune disease in animal models and has shown promise in clinical trials of type 1 diabetes. Whereas intravenous administration of CD3-specific mAb acts primarily by transient depletion of activated effector T cells, oral CD3-specific mAb acts primarily by the induction Tregs. We investigated whether oral CD3-specific mAb inhibits disease in non obese diabetic (NOD) mice that spontaneously develop autoimmune diabetes, closely resembling human type 1 diabetes...
October 10, 2016: Journal of Autoimmunity
Shu-Jing Yu, Rong Jiang, Ying Z Mazzu, Cai-Bing Wei, Zong-Liang Sun, Yu-Zhen Zhang, Lian-Di Zhou, Qi-Hui Zhang
Drug-induced liver injury (DILI) is the most common cause of acute liver failure. Disruption of the Th17/Treg balance can lead to hepatic inflammation, which causes the main symptoms of DILI. Here we investigate the protective mechanisms of (-)-Epigallocatechin-3-gallate (EGCG) on triptolide (TP)-induced DILI that shows the Th17/Treg imbalance. Pretreatment with EGCG (5[Formula: see text]mg/kg) for 10 days before TP (0.5[Formula: see text]mg/kg) administration in mice significantly reduced the increased alanine aminotransferase (ALT) level ([Formula: see text]) induced by TP treatment...
2016: American Journal of Chinese Medicine
Anders Dige, Tue Kruse Rasmussen, Peter Nejsum, Rikke Hagemann-Madsen, Andrew R Williams, Jørgen Agnholt, Jens F Dahlerup, Christian L Hvas
Helminthic therapy of immune-mediated diseases has gained attention in recent years, but we know little of how helminths modulate human immunity. In this study, we investigated how self-infection with Trichuris (T.) trichiura in an adult man without intestinal disease affected mucosal and systemic immunity. Colonic mucosal biopsies were obtained at baseline, during T. trichiura infection, and after its clearance following mebendazole treatment. Unexpectedly, the volunteer experienced a Campylobacter colitis following T...
October 15, 2016: Parasite Immunology
Maggie L Diller, Ragini R Kudchadkar, Keith A Delman, David H Lawson, Mandy L Ford
Th17 cells represent a distinct subset of CD4 effector T cells with potent pathogenic qualities, capable of directly mediating tumor cell destruction. IL-2 has frequently been shown to have a negative effect on Th17 differentiation while supporting regulatory T-cell (FoxP3CD4, TREG) growth and development in both in vitro models and in vivo animal models. We investigated the effect of in vivo IL-2 on both the Th17 and FoxP3CD4 T-cell compartments in a human model of cancer. High-dose IL-2 (HDIL-2) was administered at a dose of 720,000 IU/kg to patients with melanoma (n=7) and peripheral blood was collected at baseline and at 24, 48, 72, and 96 hours posttreatment...
November 2016: Journal of Immunotherapy
Siri Tähtinen, Carolin Blattner, Markus Vähä-Koskela, Dipongkor Saha, Mikko Siurala, Suvi Parviainen, Jochen Utikal, Anna Kanerva, Viktor Umansky, Akseli Hemminki
The immunosuppressive microenvironment of solid tumors renders adoptively transferred T cells hypofunctional. However, adenoviral delivery of immunostimulatory cytokines IL2 and TNFα can significantly improve the efficacy of adoptive T-cell therapy. Using ret transgenic mice that spontaneously develop skin malignant melanoma, we analyzed the mechanism of action of adenoviruses coding for IL2 and TNFα in combination with adoptive transfer of TCR-transgenic TRP-2-specific T cells. Following T-cell therapy and intratumoral virus injection, a significant increase in antigen-experienced, tumor-reactive PD-1 CD8 T cells was seen in both cutaneous lesions and in metastatic lymph nodes...
November 2016: Journal of Immunotherapy
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