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Helios immunity

Eleonora Timperi, Ilenia Pacella, Valeria Schinzari, Chiara Focaccetti, Luca Sacco, Francesco Farelli, Roberto Caronna, Gabriella Del Bene, Flavia Longo, Antonio Ciardi, Sergio Morelli, Anna Rita Vestri, Piero Chirletti, Vincenzo Barnaba, Silvia Piconese
Tregs can contribute to tumor progression by suppressing antitumor immunity. Exceptionally, in human colorectal cancer (CRC), Tregs are thought to exert beneficial roles in controlling pro-tumor chronic inflammation. The goal of our study was to characterize CRC-infiltrating Tregs at multiple levels, by phenotypical, molecular and functional evaluation of Tregs from the tumor site, compared to non-tumoral mucosa and peripheral blood of CRC patients. The frequency of Tregs was higher in mucosa than in blood, and further significantly increased in tumor...
July 2016: Oncoimmunology
Duke Geem, Vu Ngo, Akihito Harusato, Benoit Chassaing, Andrew T Gewirtz, Rodney D Newberry, Timothy L Denning
: This study showed that the absence of CCR7 or mesenteric lymph nodes/gut-associated lymphoid tissue did not appreciably impact total intestinal Foxp3+ regulatory T cell representation in the steady-state. However, mesenteric lymph nodes/GALT are required for normal peripherally induced Foxp3+ regulatory T cell differentiation in the small intestine, but not in the large intestine. BACKGROUND & AIMS: Foxp3+ regulatory T cells (Tregs) in the intestine promote immune tolerance to enteric antigens...
May 2016: Cellular and Molecular Gastroenterology and Hepatology
Jincao Tang, Renjie Yang, Ling Lv, Aihua Yao, Liyong Pu, Aihong Yin, Xiangcheng Li, Yue Yu, Scott L Nyberg, Xuehao Wang
Acute rejection is commonly encountered for long-term survival in liver transplant (LT) recipients and may impact their long-term survival if rejection is severe or recurrent. The aim of this study is to examine the therapeutic potential of transforming growth factor (TGF-β)-overexpressing mesenchymal stem cells (MSCs) in inducing a local immunosuppression in liver grafts after transplantation. MSCs were transduced with a lentiviral vector expressing the human TGF-β1 gene; TGF-β1-overexpressing MSCs (designated as TGF/MSCs) were then transfused into the liver grafts via the portal vein of a rat LT model of acute rejection...
June 22, 2016: Stem Cells
Natália Prearo Moço, Laura Fernandes Martin, Bruna Ribeiro de Andrade Ramos, Rodrigo Paupério Soares de Camargo, Stephanno Gomes Pereira Sarmento, Karayna Gil Fernandes, Dionísio Chiaratto Filho, Hélio Amante Miot, Márcia Guimarães da Silva
BACKGROUND: Triggering receptors expressed on myeloid cells-1 (TREM-1) are innate immune receptors that mediate inflammatory response. In recent times, the role of these receptors has become the focus of several studies in the gestational context. Evaluation of soluble TREM-1 concentration in normal pregnancy is scarce, and no data are available on the levels of this receptor in the last weeks of normal pregnancy. METHOD: Amniotic fluid (AF) samples were obtained from 77 patients in the last weeks of normal pregnancy during cesarean section, and the soluble form of TREM-1 (sTREM-1) levels determined using specific sandwich enzyme-linked immunosorbent assay kit...
June 8, 2016: Gynecologic and Obstetric Investigation
Xuehui He, Sija Landman, Stijn C G Bauland, Juliette van den Dolder, Hans J P M Koenen, Irma Joosten
Regulatory T cells (Treg) are important for immune homeostasis and are considered of great interest for immunotherapy. The paucity of Treg numbers requires the need for ex vivo expansion. Although therapeutic Treg flow-sorting is feasible, most centers aiming at Treg-based therapy focus on magnetic bead isolation of CD4+CD25+ Treg using a good manufacturing practice compliant closed system that achieves lower levels of cell purity. Polyclonal Treg expansion protocols commonly use anti-CD3 plus anti-CD28 monoclonal antibody (mAb) stimulation in the presence of rhIL-2, with or without rapamycin...
2016: PloS One
Laurent Beziaud, Laura Mansi, Patrice Ravel, Elodie Lauret Marie-Joseph, Caroline Laheurte, Laurie Rangan, Francis Bonnefoy, Jean-René Pallandre, Laura Boullerot, Clémentine Gamonet, Sindy Vrecko, Lise Queiroz, Tristan Maurina, Guillaume Mouillet, Thierry Nguyen Tan Hon, Elsa Curtit, Bernard Royer, Béatrice Gaugler, Jagadeesh Bayry, Eric Tartour, Antoine Thiery-Vuillemin, Xavier Pivot, Christophe Borg, Yann Godet, Olivier Adotévi
The rapalogs everolimus and temsirolimus that inhibit mTOR signaling are used as antiproliferative drugs in several cancers. Here we investigated the influence of rapalogs-mediated immune modulation on their antitumor efficacy. Studies in metastatic renal cell carcinoma patients showed that everolimus promoted high expansion of FoxP3 (+)Helios(+)Ki67(+) regulatory CD4 T cells (Tregs). In these patients, rapalogs strongly enhanced the suppressive functions of Tregs, mainly in a contact-dependent manner. Paradoxically, a concurrent activation of spontaneous tumor-specific Th1 immunity also occurred...
July 15, 2016: Cancer Research
Hidetoshi Nakagawa, Jessica M Sido, Edwin E Reyes, Valerie Kiers, Harvey Cantor, Hye-Jung Kim
Expression of the transcription factor Helios by Tregs ensures stable expression of a suppressive and anergic phenotype in the face of intense inflammatory responses, whereas Helios-deficient Tregs display diminished lineage stability, reduced FoxP3 expression, and production of proinflammatory cytokines. Here we report that selective Helios deficiency within CD4 Tregs leads to enhanced antitumor immunity through induction of an unstable phenotype and conversion of intratumoral Tregs into T effector cells within the tumor microenvironment...
May 31, 2016: Proceedings of the National Academy of Sciences of the United States of America
Carla C Baan, Nynke M Kannegieter, Claudia Rosso Felipe, Helio Tedesco Silva
The profound involvement of cytokines in allograft rejection makes the molecules that control their actions, members of the Jak-Stat pathway, ideal targets for pharmacological intervention. Numerous studies have demonstrated that Jak3 is widely involved in the activation cascade and function of most immune cells. Tofacitinib, an oral Janus kinase inhibitor that targets Jak1/Jak3 dependent Stat activation, has been assessed as a substitute for calcineurin inhibitor therapy after low-to-moderate risk kidney transplantation in 3 randomized trials...
September 2016: Transplantation
A Gibbs, E Leeansyah, A Introini, D Paquin-Proulx, K Hasselrot, E Andersson, K Broliden, J K Sandberg, A Tjernlund
The female genital tract (FGT) mucosa is a critically important site for immune defense against microbes. Mucosal-associated invariant T (MAIT) cells are an innate-like T-cell population that recognizes microbial riboflavin metabolite antigens in an MR1-dependent manner. The role of MAIT cells in the FGT mucosa is unknown. Here, we found that MAIT cells and MR1(+) antigen-presenting cells were present in the upper and lower FGT, with distinct tissue localization of MAIT cells in endometrium vs. cervix. The MAIT cells from the FGT and blood displayed a distinct phenotype with expression of interleukin (IL)-18Rα, CD127, α4β7, PD-1, as well as the transcription factors promyelocytic leukemia zinc finger (PLZF), RORγt, Helios, Eomes, and T-bet...
April 6, 2016: Mucosal Immunology
Cesar M Rueda, Pietro Presicce, Courtney M Jackson, Lisa A Miller, Suhas G Kallapur, Alan H Jobe, Claire A Chougnet
Chorioamnionitis is associated with preterm labor and fetal inflammatory response syndrome (FIRS), causing fetal organ injury and morbidity, particularly in extremely premature infants. However, the effects of inflammation on the fetal immune system remain poorly understood, due to the difficulty of studying immune development in infants. Therefore, we used the model of intra-amniotic LPS administered at ∼80% gestation in rhesus monkeys to cause chorioamnionitis and FIRS that is similar in human pathology...
May 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Alka Khaitan, Adam Kravietz, Mussa Mwamzuka, Fatma Marshed, Tiina Ilmet, Swalehe Said, Aabid Ahmed, William Borkowsky, Derya Unutmaz
Regulatory T cells (Tregs) are functionally suppressive CD4 T cells, critical for establishing peripheral tolerance and controlling inflammatory responses. Previous reports of Tregs during chronic HIV disease have conflicting results with higher or lower levels compared with controls. Identifying true Tregs with suppressive activity proves challenging during HIV infection, as traditional Treg markers, CD25 and FOXP3, may transiently upregulate expression as a result of immune activation (IA). Helios is an Ikaros family transcription factor that marks natural Tregs with suppressive activity and does not upregulate expression after activation...
August 15, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Jennifer Town, Helio Pais, Sally Harrison, Lucy F Stead, Carole Bataille, Wilawan Bunjobpol, Jing Zhang, Terence H Rabbitts
The cell surface proteome of tumors mediates the interface between the transformed cells and the general microenvironment, including interactions with stromal cells in the tumor niche and immune cells such as T cells. In addition, the cell surface proteome of individual cancers defines biomarkers for that tumor type and potential proteins that can be the target of antibody-mediated therapy. We have used next-generation deep RNA sequencing (RNA-seq) coupled to an in-house database of genes encoding cell surface proteins (herein referred to as the surfaceome) as a tool to define a cell surface proteome of Ewing sarcoma compared with progenitor mesenchymal stem cells...
March 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
An T T Dao, Hirohito Yamazaki, Hiroyuki Takamatsu, Chiharu Sugimori, Takamasa Katagiri, Hiroyuki Maruyama, Yoshitaka Zaimoku, Kana Maruyama, Trung Q Ly, Luis Espinoza, Shinji Nakao
Most patients with acquired pure red cell aplasia (PRCA) and some with acquired aplastic anemia (AA) respond well to cyclosporine (CsA), but thereafter often show CsA dependency. The mechanism underlying this dependency remains unknown. We established a reliable method for measuring the regulatory T cell (Treg) count using FoxP3 and Helios expression as markers and determined the balance between Tregs and other helper T cell subsets in 16 PRCA and 29 AA patients. The ratios of interferon-γ-producing CD4(+) (Th1) T cells to Tregs in untreated patients and CsA-dependent patients were significantly higher (PRCA 5...
April 2016: Annals of Hematology
Simone Abel, Kristina Ueffing, Roman Tatura, Marina Hutzler, Matthias Hose, Kai Matuschewski, Jan Kehrmann, Astrid M Westendorf, Jan Buer, Wiebke Hansen
Recently, we demonstrated elevated numbers of CD4(+) Foxp3(+) regulatory T (Treg) cells in Plasmodium yoelii-infected mice contributing to the regulation of anti-malarial immune response. However, it remains unclear whether this increase in Treg cells is due to thymus-derived Treg cell expansion or induction of Treg cells in the periphery. Here, we show that the frequency of Foxp3(+) Treg cells expressing neuropilin-1 (Nrp-1) decreased at early time-points during P. yoelii infection, whereas percentages of Helios(+) Foxp3(+) Treg cells remained unchanged...
June 2016: Immunology
Sophia Björkander, Lena Hell, Maria A Johansson, Manuel Mata Forsberg, Gintare Lasaviciute, Stefan Roos, Ulrika Holmlund, Eva Sverremark-Ekström
Staphylococcus aureus (S. aureus) is a human pathogen as well as a frequent colonizer of skin and mucosa. This bacterium potently activates conventional T-cells through superantigens and it is suggested to induce T-cell cytokine-production as well as to promote a regulatory phenotype in T-cells in order to avoid clearance. This study aimed to investigate how S. aureus impacts the production of regulatory and pro-inflammatory cytokines and the expression of CD161 and HELIOS by peripheral CD4(+)FOXP3(+) T-cells...
2016: Scientific Reports
P Ramos-Ramírez, C Malmhäll, K Johansson, J Lötvall, A Bossios
Adipose tissue produces multiple mediators that modulate the immune response. Adiponectin is an adipocyte-derived cytokine that exhibits metabolic and anti-inflammatory effects. Adiponectin acts through binding to adiponectin receptor 1 and 2 (AdipoR1/AdipoR2). AdipoR1 is ubiquitously expressed, whereas AdipoR2 is restricted to skeletal muscle and liver. AdipoR1 expression has been reported on a small percentage of T cells; nevertheless, it is still unknown whether Foxp3(+) regulatory T cells (Tregs) express AdipoR1...
April 2016: Scandinavian Journal of Immunology
Lucia De Monte, Sonja Wörmann, Emanuela Brunetto, Silvia Heltai, Gilda Magliacane, Michele Reni, Anna Maria Paganoni, Helios Recalde, Anna Mondino, Massimo Falconi, Francesca Aleotti, Gianpaolo Balzano, Hana Algül, Claudio Doglioni, Maria Pia Protti
In pancreatic ductal adenocarcinomas (PDAC), lymphoid infiltrates, comprised mainly of Th2 cells, predict a poor survival outcome in patients. IL4 signaling has been suggested to stabilize the Th2 phenotype in this setting, but the cellular source of IL4 in PDAC is unclear. Here, we show that basophils expressing IL4 are enriched in tumor-draining lymph nodes (TDLN) of PDAC patients. Basophils present in TDLNs correlated significantly with the Th2/Th1 cell ratio in tumors, where they served as an independent prognostic biomarker of patient survival after surgery...
April 1, 2016: Cancer Research
Christina Ballke, Einar Gran, Espen S Baekkevold, Frode L Jahnsen
CD4+ T regulatory cells (Tregs) comprise a heterogeneous population of cells the regulate immune responses and prevent autoimmunity. Most reports on human Tregs are derived from studies of peripheral blood, although Tregs mainly exert their functions in the periphery. Here we performed a detailed analysis of Tregs in the human upper airway mucosa under non-inflammatory conditions, and found that 10% of all CD4+ T cells expressed the transcription factor FOXP3 and the memory marker CD45RO, as well as high levels of CTLA-4...
2016: PloS One
Josef Yayan, Kurt Rasche
Older people are often especially susceptible to pneumonia and bacteria may develop resistance to antibiotics quicker in the elderly, whose immune systems gradually diminish. This study analyses, retrospectively, resistance to antibiotics in high-risk elderly patients with fatal pneumonia. Records of all patients aged over 65 who did not survive a bout with pneumonia were gathered from the records of the Department of Pneumology of HELIOS Clinic in Wuppertal, Germany from the period of 2004-2014. Susceptibility testing was executed for the study population, whose pneumonia was triggered by various kinds of bacteria...
2016: Advances in Experimental Medicine and Biology
Kanako Saito, Pascale Pignon, Maha Ayyoub, Danila Valmori
CD4 T cells secreting IL-10 or IL-17 are frequent at mucosal sites, where their equilibrium is important for simultaneously maintaining tolerance and immunity to the resident microbiota. The mode of action of these cells, however, is as yet incompletely understood. In this study, we have combined ex vivo analysis of CD4 T cells producing IL-10 or/and IL-17 with assessment of clonal populations isolated ex vivo using a cytokine catch assay. We found that circulating CD4 T cells secreting IL-10 or/and IL-17 ex vivo include both conventional FOXP3- CD4 T cells and FOXP3+ Helios- Treg...
2015: PloS One
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