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Foxp3, treg,

Flore Amat, Pauline Tallon, Anne-Perrine Foray, Bénédicte Michaud, Nathalie Lambert, Philippe Saint-Pierre, Lucienne Chatenoud, Jocelyne Just
Allergic asthma is an inflammatory disease of the airways, resulting from an inappropriate immune response to inhaled allergens, which involves multiple inflammatory cells and mediators that contribute to airway hyper-responsiveness. Omalizumab is a monoclonal antibody, specifically directed to the C-Epsilon3 domain of immunoglobulin E (IgE), indicated as an additional therapy in severe allergic asthma [1]. Impaired function of regulatory T cells (Treg) is incriminated in the aberrant asthma inflammatory response [2]...
October 22, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Xiaodan Luo, Lihua Xu, Yangqiu Li, Huo Tan
Graft-versus-host disease (GVHD) induced by host antigen-presenting cells (APCs) and donor-derived T cells remains the major limitation of allogeneic bone marrow transplantation (allo-BMT). Notch signaling pathway is a highly conserved cell-cell communication that is important in T cell development. Recently, Notch signaling pathway is reported to be involved in regulating GVHD. To investigate the role of Notch inhibition in modulating GVHD, we established MHC-mismatched murine allo-BMT model. We found that inhibition of Notch signaling pathway by γ-secretase inhibitor in vivo could reduce aGVHD, which was shown by the onset time of aGVHD, body weight, clinical aGVHD scores, pathology aGVHD scores, and survival...
October 21, 2016: Cell Biology and Toxicology
Liqing Wang, Suresh Kumar, Satinder Dahiya, Feng Wang, Jian Wu, Kheng Newick, Rongxiang Han, Arabinda Samanta, Ulf H Beier, Tatiana Akimova, Tricia R Bhatti, Benjamin Nicholson, Mathew P Kodrasov, Saket Agarwal, David E Sterner, Wei Gu, Joseph Weinstock, Tauseef R Butt, Steven M Albelda, Wayne W Hancock
Foxp3+ T-regulatory (Treg) cells are known to suppress protective host immune responses to a wide variety of solid tumors, but their therapeutic targeting is largely restricted to their transient depletion or "secondary" modulation, e.g. using anti-CTLA-4 monoclonal antibody. Our ongoing studies of the post-translational modifications that regulate Foxp3 demonstrated that the histone/protein acetyltransferase, Tip60, plays a dominant role in promoting acetylation, dimerization and function in Treg cells. We now show that the ubiquitin-specific protease, Usp7, controls Treg function largely by stabilizing the expression and promoting the multimerization of Tip60 and Foxp3...
October 15, 2016: EBioMedicine
Su-Min Lim, Hyun Sik Choi, Jin-Ju Jeong, Seung-Won Han, Dong-Hyun Kim
We investigated the effect of DWac on the gut microbiota composition in mice with 2,3,6-trinitrobenzenesulfonic acid- (TNBS-) induced colitis. Treatment with DWac restored TNBS-disturbed gut microbiota composition and attenuated TNBS-induced colitis. Moreover, we examined the effect of DWac in mice with mesalazine-resistant colitis (MRC). Intrarectal injection of TNBS in MRC mice caused severe colitis, as well as colon shortening, edema, and increased myeloperoxidase activity. Treatment with mesalazine (30 mg/kg) did not attenuate TNBS-induced colitis in MRC mice, whereas treatment with DWac (30 mg/kg) significantly attenuated TNBS-induced colitis...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Monika Ryba-Stanisławowska, Paulina Werner, Maria Skrzypkowska, Agnieszka Brandt, Jolanta Myśliwska
IL-33 is an IL-1 cytokine family member, with ability to induce both Th1 and Th2 immune responses. It binds to ST2 receptor, whose deficiency is associated with enhanced inflammatory response. The most recent studies have shown the immunoregulatory effect of IL-33 on Tregs in animal models. As type 1 diabetes is an autoimmune, inflammatory disease, where Treg defects have been described, we aimed to analyze the in vitro influence of recombinant IL-33 on quantitative properties of regulatory CD4(+)CD25(high)FOXP3(+) T cells...
2016: Mediators of Inflammation
Hidekazu Nishikii, Byung-Su Kim, Yasuhisa Yokoyama, Yan Chen, Jeanette Baker, Antonio Pierini, Maite Alvarez, Melissa Mavers, Kristina Maas-Bauer, Yuqiong Pan, Shigeru Chiba, Robert S Negrin
CD4(+)Foxp3(+) regulatory T cells (Treg) are a subpopulation of T cells, which regulate the immune system and enhance immune tolerance after transplantation. Donor-derived Treg prevent the development of lethal acute graft versus host disease (GVHD) in murine models of allogeneic hematopoietic stem cell transplantation (HCT). We recently demonstrated that a single treatment of the agonistic antibody to DR3 (Death receptor 3, αDR3) to donor mice resulted in the expansion of donor derived Treg and prevented acute GVHD, although the precise role of DR3 signaling in GVHD has not been elucidated...
October 19, 2016: Blood
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
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
Naoyuki Makita, Jun Ishiguro, Keisuke Suzuki, Futoshi Nara
OBJECTIVES: Recently, there has been a growing interest in the mechanism of action of dichloroacetate (DCA) for T-cell differentiation; however, this mechanism has not been elucidated in detail. Therefore, this study aimed to investigate the mechanism of action of DCA for Treg and Th17 differentiation with pyruvate dehydrogenase kinase (PDHK) inhibitor (AZD7545) and PDHK knockdown. METHODS: Inhibitory activity of DCA and AZD7545 against recombinant PDHK and intracellular PDH phosphorylation was measured...
October 19, 2016: Journal of Pharmacy and Pharmacology
Edurne Arriola, Matthew Wheater, Maria Antonette Lopez, Gareth Thomas, Christian Ottensmeier
Approximately 30% of patients treated with ipilimumab will develop gastrointestinal toxicity. The immunological drivers that underpin the clinical observations in human tissues are poorly understood. We report here on the immune consequences of ipilimumab treatment in the colorectal mucosa of patients with treatment-related colitis. Using immunohistochemistry, we evaluated the immune infiltrate by CD8(+), FoxP3, and granzyme B (GzmB) in colonic biopsies from 20 patients with ipilimumab-related colitis. We assessed 10 cases with normal colon biopsies for comparison...
2016: Oncoimmunology
Ryoyo Ikebuchi, Shunsuke Teraguchi, Alexis Vandenbon, Tetsuya Honda, Francis H W Shand, Yasutaka Nakanishi, Takeshi Watanabe, Michio Tomura
Foxp3(+) regulatory T cells (Tregs) migrating from the skin to the draining lymph node (dLN) have a strong immunosuppressive effect on the cutaneous immune response. However, the subpopulations responsible for their inhibitory function remain unclear. We investigated single-cell gene expression heterogeneity in Tregs from the dLN of inflamed skin in a contact hypersensitivity model. The immunosuppressive genes Ctla4 and Tgfb1 were expressed in the majority of Tregs. Although Il10-expressing Tregs were rare, unexpectedly, the majority of Il10-expressing Tregs co-expressed Gzmb and displayed Th1-skewing...
October 19, 2016: Scientific Reports
Hirotsugu Nagase, Tomohira Takeoka, Shinya Urakawa, Akiko Morimoto-Okazawa, Atsunari Kawashima, Kota Iwahori, Shuji Takiguchi, Hiroyoshi Nishikawa, Eiichi Sato, Shimon Sakaguchi, Masaki Mori, Yuichiro Doki, Hisashi Wada
Regulatory T cells (Tregs) have an immunosuppressive role in the tumor microenvironment. Since effector Tregs (eTregs), which have highly suppressive functions, are located in a subpopulation of Foxp3(+) CD4(+) Tregs, the TCR-inducible costimulatory receptor (ICOS) was applied as a marker of eTregs that infiltrated gastric cancer tissue and the induction pathway of ICOS(+) Foxp3(+) cells was analyzed by flow cytometry and immunohistochemistry. In tumor-infiltrating lymphocytes (TILs), ICOS(+) Foxp3(+) CD4(+) T cells were abundantly observed in the late stages of gastric cancer...
October 18, 2016: International Journal of Cancer. Journal International du Cancer
Lingran Kong, Chengchao Ruan, Pingjin Gao
OBJECTIVE: Inflammatory processes plays a pivotal role in pathogenesis of hypertension. Previous study have indicated that A2A receptor is closely related with immunogenic anti-inflammation process. The present study aimed to elucidate whether the activation of A2A receptor is involved in the regulation of hypertension-induced cardiovascular consequence via regulating immunoresponse. DESIGN AND METHOD: Deoxycorticosterone acetat (DOCA)-salt hypertensive mice were injected intraperitoneally with specific A2A receptor agonist (CGS21680) or antagonist (istradefylline) or PBS respectively...
September 2016: Journal of Hypertension
Myung-Shik Lee
Low-grade systemic inflammation in adipose tissues or liver, is an important etiologic factor in insulin resistance. LPS is an important element causing such metabolic inflammation, and intestinal flora is considered a major source of systemic LPS. We studied changes of intestinal microbiota associated with high-fat diet (HFD) that causes insulin resistance and metabolic stress. 16S rRNA gene sequencing showed that HFD significantly decreased the abundance of a mucin-degrading bacterium Akkermansia muciniphila compared to control diet...
September 2016: Journal of Hypertension
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
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
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
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