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T M Fenton, A Kelly, E E Shuttleworth, C Smedley, A Atakilit, F Powrie, S Campbell, S L Nishimura, D Sheppard, S Levison, J J Worthington, M J Lehtinen, M A Travis
Regulation of intestinal T-cell responses is crucial for immune homeostasis and prevention of inflammatory bowel disease (IBD). A vital cytokine in regulating intestinal T cells is transforming growth factor-β (TGFβ), which is secreted by cells as a latent complex that requires activation to function. However, how TGFβ activation is regulated in the human intestine, and how such pathways are altered in IBD is completely unknown. Here we show that a key activator of TGFβ, integrin αvβ8, is highly expressed on human intestinal dendritic cells (DCs), specifically on the CD1c(+) but not the CD141(+) intestinal DC subset...
October 26, 2016: Mucosal Immunology
Angelika Drynda, Bożena Obmińska-Mrukowicz, Ewa Zaczyńska, Michał Zimecki, Stanisław Ryng, Marcin Mączyński
OBJECTIVES: Immunoregulatory properties of 06K derivative (4-(4-chlorophenyl)-1-(5-amino-3-methylisoxazole-4-carbonyl)-thiosemicarbazide) in mouse in vivo models were investigated. METHODS: Several in vivo models were used: humoral and cellular immune response, carrageenan inflammatory reaction and determination of lymphocyte subsets in non-immunized mice. KEY FINDINGS: The compound administered before or after immunization with sheep erythrocytes (sheep red blood cell (SRBC)) elevated the number of plaque-forming cells (PFC), and this effect was stronger at lower doses...
October 26, 2016: Journal of Pharmacy and Pharmacology
Isolde G Rojas, Maria L Spencer, Paulina A Zapata, Alejandra Martínez, Rosario Alarcón, Francisco J Marchesani, Mine Tezal
BACKGROUND: Differences in immune profile between actinic cheilitis (AC), a precursor of lip squamous cell carcinoma, and normal lip vermillion (NL) have not been elucidated. OBJECTIVES: To compare density, distribution, and ratios of CD8+ and FoxP3+ cells between AC and NL and assess their associations with clinicopathologic variables. METHODS: Samples of AC and NL obtained between 2001 and 2013 at the College of Dentistry of the University of Concepcion, Chile, were retrospectively analyzed for immunohistochemical detection of CD8+ and FoxP3+ cells...
October 25, 2016: International Journal of Dermatology
Hee Yeon Won, Eun Sook Hwang
Regulatory T (Treg) cells with high expression of both CD25 and Foxp3 are developed in the thymus and also peripheral tissues. Treg cells suppress the activation and functions of effector T cells raised against specific antigens and are crucial for maintaining immune homeostasis. Treg cell development is associated with the induction of and epigenetic alterations of forkhead transcription factor Foxp3. Foxp3 expression is increased by the activation of several transcription factors including nuclear factor-kappa B (NF-κB), nuclear factor of activated T cells (NFAT), and Smad3 in response to various signals such as TGFβ, retinoic acid, and rapamycin...
October 25, 2016: Archives of Pharmacal Research
Viriya Kaewkangsadan, Chandan Verma, Jennifer M Eremin, Gerard Cowley, Mohammed Ilyas, Oleg Eremin
The tumour microenvironment consists of malignant cells, stroma, and immune cells. Prominent tumour-infiltrating lymphocytes (TILs) in breast cancer are associated with a good prognosis and are predictors of a pathological complete response (pCR) with neoadjuvant chemotherapy (NAC). The contribution of different T effector/regulatory cells and cytokines to tumour cell death with NAC requires further characterisation and was investigated in this study. Breast tumours from 33 women with large and locally advanced breast cancers undergoing NAC were immunohistochemically (intratumoural, stromal) assessed for T cell subsets and cytokine expression using labelled antibodies, employing established semiquantitative methods...
2016: Journal of Immunology Research
Yong-Chao Qiao, Jian Shen, Lan He, Xue-Zhi Hong, Fang Tian, Yan-Hong Pan, Ling Liang, Xiao-Xi Zhang, Hai-Lu Zhao
Objective. The aim of this study was to investigate the changes of regulatory T cells (Treg), interleukin-6 (IL-6), IL-10, transforming growth factor-β (TGF-β), and tumor necrosis factor-alpha (TNF-α) in patients with type 2 diabetes mellitus (T2DM). Methods. We performed a comprehensive search up to July 2016 for all clinical studies about the changes of Treg, IL-6, IL-10, IL-17, TGF-β, and TNF-α in T2DM patients versus healthy controls. Results. A total of 91 articles (5642 cases and 7378 controls) were included for this meta-analysis...
2016: Journal of Diabetes Research
Carlos A Castaneda, Elizabeth Mittendorf, Sandro Casavilca, Yun Wu, Miluska Castillo, Patricia Arboleda, Teresa Nunez, Henry Guerra, Carlos Barrionuevo, Ketty Dolores-Cerna, Carolina Belmar-Lopez, Julio Abugattas, Gabriela Calderon, Miguel De La Cruz, Manuel Cotrina, Jorge Dunstan, Henry L Gomez, Tatiana Vidaurre
AIM: To determine influence of neoadjuvant-chemotherapy (NAC) over tumor-infiltrating-lymphocytes (TIL) in triple-negative-breast-cancer (TNBC). METHODS: TILs were evaluated in 98 TNBC cases who came to Instituto Nacional de Enfermedades Neoplasicas from 2005 to 2010. Immunohistochemistry staining for CD3, CD4, CD8 and FOXP3 was performed in tissue microarrays (TMA) sections. Evaluation of H/E in full-face and immunohistochemistry in TMA sections was performed in pre and post-NAC samples...
October 10, 2016: World Journal of Clinical Oncology
Sasha E Stanton, Mary L Disis
Tumor infiltrating lymphocytes (TIL) play an essential role in mediating response to chemotherapy and improving clinical outcomes in all subtypes of breast cancer. Triple negative breast cancers (TN) are most likely to have tumors with >50 % lymphocytic infiltrate, termed lymphocyte predominant breast cancer, and derive the greatest survival benefit from each 10 % increase in TIL. The majority of HER2(+) breast cancers have similar level of immune infiltrate as TN breast cancer yet the presence of TILs has not shown the same survival benefit...
2016: Journal for Immunotherapy of Cancer
Kristian Tonby, Ida Wergeland, Nora V Lieske, Dag Kvale, Kjetil Tasken, Anne M Dyrhol-Riise
BACKGROUND: Tuberculosis (TB) causes a major burden on global health with long and cumbersome TB treatment regimens. Host-directed immune modulating therapies have been suggested as adjunctive treatment to TB antibiotics. Upregulated cyclooxygenase-2 (COX-2)-prostaglandin E2 (PGE2) signaling pathway may cause a dysfunctional immune response that favors survival and replication of Mycobacterium tuberculosis (Mtb). METHODS: Blood samples were obtained from patients with latent TB (n = 9) and active TB (n = 33) before initiation of anti-TB chemotherapy...
October 24, 2016: BMC Infectious Diseases
Dana Tedesco, Manoj Thapa, Sanjeev Gumber, Elizabeth J Elrod, Khalidur Rahman, Chris C Ibegbu, Joseph F Magliocca, Andrew B Adams, Frank Anania, Arash Grakoui
: Persistent hepatotropic viral infections are a common etiologic agent of chronic liver disease. Unresolved infection can be attributed to non-functional intrahepatic CD8+ T cell responses. In light of dampened CD8+ T cell responses, liver disease often manifests systemically as Ig-related syndromes due to aberrant B cell functions. These two opposing yet co-existing phenomena implicate the potential of altered CD4+ T cell help. Elevated CD4+ Foxp3+ T cells were evident in both human liver disease and a mouse model of chemically induced liver injury despite marked activation and spontaneous IgG production by intrahepatic B cells...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Petra Bacher, Frederik Heinrich, Ulrik Stervbo, Mikalai Nienen, Marco Vahldieck, Christina Iwert, Katrin Vogt, Jutta Kollet, Nina Babel, Birgit Sawitzki, Carsten Schwarz, Stefan Bereswill, Markus M Heimesaat, Guido Heine, Gabriele Gadermaier, Claudia Asam, Mario Assenmacher, Olaf Kniemeyer, Axel A Brakhage, Fátima Ferreira, Michael Wallner, Margitta Worm, Alexander Scheffold
FOXP3+ regulatory T cells (Tregs) maintain tolerance against self-antigens and innocuous environmental antigens. However, it is still unknown whether Treg-mediated tolerance is antigen specific and how Treg specificity contributes to the selective loss of tolerance, as observed in human immunopathologies such as allergies. Here, we used antigen-reactive T cell enrichment to identify antigen-specific human Tregs. We demonstrate dominant Treg-mediated tolerance against particulate aeroallergens, such as pollen, house dust mites, and fungal spores...
October 18, 2016: Cell
Denise Mathes, Johannes Weirather, Peter Nordbeck, Anahi-Paula Arias-Loza, Matthias Burkard, Christina Pachel, Thomas Kerkau, Niklas Beyersdorf, Stefan Frantz, Ulrich Hofmann
OBJECTIVE: The present study analyzed the effect of CD4(+) Forkhead box protein 3 negative (Foxp3(-)) T-cells and Foxp3(+) CD4(+) T-cells on infarct size in a mouse myocardial ischemia-reperfusion model. APPROACH AND RESULTS: We examined the infarct size as a fraction of the area-at-risk as primary study endpoint in mice after 30minutes of coronary ligation followed by 24hours of reperfusion. CD4(+) T-cell deficient MHC-II KO mice showed smaller histologically determined infarct size (34...
October 19, 2016: Journal of Molecular and Cellular Cardiology
J Fotschki, A M Szyc, J M Laparra, L H Markiewicz, B Wróblewska
The aim of this study was to examine immune adaptive changes, the expression of innate biomarkers and variations in intestinal microbiota composition after horse-milk administration in BALB/c mice, which were sensitized intraperitoneally using cow β-lactoglobulin and α-casein with aluminum adjuvant. We measured serum antibody IgE levels and the expression of MCP-1, IL-4, and TNF-α in duodenal samples. Changes in immune cell populations in peripheral blood were quantified using flow cytometry, and intestinal microbiota composition was assessed using real-time PCR...
October 19, 2016: Journal of Dairy Science
Shanzheng Lu, Ganggang Shi, Xiaoxi Xu, Grace Wang, Xu Lan, Peng Sun, Xiang Li, Baoren Zhang, Xiangying Gu, Thomas E Ichim, Hao Wang
BACKGROUND: The endometrial regenerative cell (ERC) is a novel type of adult mesenchymal stem cell isolated from menstrual blood. Previous studies demonstrated that ERCs possess unique immunoregulatory properties in vitro and in vivo, as well as the ability to differentiate into functional hepatocyte-like cells. For these reasons, the present study was undertaken to explore the effects of ERCs on carbon tetrachloride (CCl4)-induced acute liver injury (ALI). METHODS: An ALI model in C57BL/6 mice was induced by administration of intraperitoneal injection of CCl4...
October 22, 2016: Journal of Translational Medicine
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
Luciana Nahar Dos Santos, Pedro Henrique Lopes da Silva, Iris Maria Peixoto Alvim, José Augusto da Costa Nery, Flávio Alves Lara, Euzenir Nunes Sarno, Danuza Esquenazi
In spite of hyporesponsivity to Mycobacterium leprae, borderline lepromatous (BL) patients show clinical and immunological instability, and undergo frequent acute inflammatory episodes such as type 1 reaction (T1R), which may cause nerve damages. This work focused on the participation of T cell subsets from blood and skin at T1R onset. We observed a significantly increased ex vivo frequency of both effector and memory CD4+ and CD8+ T cells in T1R group. Besides, ex vivo frequency of T cell homing receptor, the Cutaneous Leukocyte-associated Antigen (CLA) was significantly increased in T cells from T1R patients...
2016: PloS One
Jing Jiao, Rongxiang Han, Wayne W Hancock, Ulf H Beier
Determining protein acetylation by immunoprecipitation and immunoblotting can be challenging, especially if the tissue of interest is low in quantity, and when good quality acetylation site-specific antibodies are not available. Proximity ligation assays allow a sensitive and quantitative method to assess Foxp3 acetylation in regulatory T cells, with as little as 1.5 × 10(5) cells within two days turnaround time. This method is of potential use in other similar scenarios, when post-translational modifications of a protein of interest need to be determined with only a small amount of sample and in the absence of specific antibodies that can assess the post-translational modification in the protein of interest...
2017: Methods in Molecular Biology
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
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