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Vanja Lundberg, Martin Berglund, Gabriel Skogberg, Susanne Lindgren, Christina Lundqvist, Judith Gudmundsdottir, Karolina Thörn, Esbjörn Telemo, Olov Ekwall
Extensive knowledge has been gained the last years concerning mechanisms underlying the selection of single positive thymocytes in the thymic medulla. Less is known regarding other important processes in the thymic medulla such as the regulation of late stage thymocyte maturation. We have previously reported that exosomes are abundant in the thymus with a phenotype that indicates an epithelial cell origin and immunoregulatory properties. In this study we use an in vitro system to investigate the effects of thymic exosomes on the maturation of single positive thymocytes as well as effects on nTreg formation...
November 8, 2016: Scientific Reports
Anne-Hilde Muris, Joost Smolders, Linda Rolf, Marielle Thewissen, Raymond Hupperts, Jan Damoiseaux
Multiple sclerosis (MS) is characterized by a disturbed immune homeostasis and low serum vitamin D levels are associated with an increased disease activity. While vitamin D has been hypothesized to promote the maintenance of immune homeostasis, vitamin D supplementation could be of benefit to patients with MS. The SOLAR study investigated the effects of high dose vitamin D3 supplementation on clinical outcomes in a randomized controlled trial. Here we present the immune regulatory effects, investigated in the SOLARIUM sub-study...
November 15, 2016: Journal of Neuroimmunology
Jessica Heinrichs, David Bastian, Anandharaman Veerapathran, Claudio Anasetti, Brain Betts, Xue-Zhong Yu
Graft-versus-host disease (GVHD) is a significant cause of non-relapse mortality after allogeneic hematopoietic cell transplantation (allo-HCT). Existing strategies to prevent and treat GVHD are incomplete, where a significant portion of allo-HCT recipients developed this complication. Despite this, one such therapy has emerged involving the use of regulatory T cells (Tregs) to control GVHD. The use of natural Tregs (nTregs) yielded positive pre-clinical results and are actively under investigation to reduce GVHD...
2016: Journal of Immunology Research and Therapy
Diamanda Rigas, Gavin Lewis, Jennifer L Aron, Bowen Wang, Homayon Banie, Ishwarya Sankaranarayanan, Lauriane Galle-Treger, Hadi Maazi, Richard Lo, Gordon J Freeman, Arlene H Sharpe, Pejman Soroosh, Omid Akbari
BACKGROUND: Atopic diseases, including asthma, exacerbate type 2 immune responses and involve a number of immune cell types, including regulatory T (Treg) cells and the emerging type 2 innate lymphoid cells (ILC2s). Although ILC2s are potent producers of type 2 cytokines, the regulation of ILC2 activation and function is not well understood. OBJECTIVE: In the present study, for the first time, we evaluate how Treg cells interact with pulmonary ILC2s and control their function...
October 4, 2016: Journal of Allergy and Clinical Immunology
Sudhir Kumar, Jiang Wang, Angus W Thomson, Chandrashekhar R Gandhi
Immunosuppressive, naturally occurring CD4(+)CD25(+)forkhead box p3(+) (Foxp3(+)) regulatory T cells (nTregs) offer potential for the treatment of immune-mediated inflammatory disorders. However, potential instability of ex vivo-expanded nTregs following their adoptive transfer may be a significant limitation. LPS-stimulated hepatic stellate cells (HSCs) induce expansion and enhance the suppressive function and stability of allogeneic nTregs We aimed to delineate mechanisms underlying HSC-induced expansion and increased potency of nTregs HSCs and nTregs were isolated from mouse livers and spleens, respectively...
August 31, 2016: Journal of Leukocyte Biology
Maria Rodi, Nikolaos Dimisianos, Anne-Lise de Lastic, Panagiota Sakellaraki, George Deraos, John Matsoukas, Panagiotis Papathanasopoulos, Athanasia Mouzaki
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) of autoimmune etiology that results from an imbalance between CNS-specific T effector cells and peripheral suppressive mechanisms mediated by regulatory cells (RC). In this research, we collected blood samples from 83 relapsing remitting MS (RRMS) patients and 45 healthy persons (HC), to assess the sizes of their RC populations, including CD4⁺CD25(high)Foxp3⁺ (nTregs), CD3⁺CD4⁺HLA(-)G⁺, CD3⁺CD8⁺CD28(-), CD3⁺CD56⁺, and CD56(bright) cells, and how RC are affected by disease activity (acute phase or remission) and types of treatment (methylprednisolone, interferon, or natalizumab)...
2016: International Journal of Molecular Sciences
Anthony Joetham, Michaela Schedel, Brian P O'Connor, Soohyun Kim, Katsuyuki Takeda, Jordan Abbott, Erwin W Gelfand
BACKGROUND: T regulatory cells attenuate development of asthma in wild-type (WT) mice with both naturally occurring (nTregs) and inducible T regulatory cells (iTregs) exhibiting suppressive activity. When transferred into CD8-deficient (CD8(-/-)) recipients, both cell types enhanced development of allergen-induced airway hyperresponsiveness (AHR). OBJECTIVE: To determine if the pathways leading to enhancement of lung allergic responses by transferred nTregs and iTregs differed...
August 16, 2016: Journal of Allergy and Clinical Immunology
Luciana Bento-de-Souza, Jefferson R Victor, Luiz C Bento-de-Souza, Magaly Arrais-Santos, Andréia C Rangel-Santos, Érica Pereira-Costa, Elaine Raniero-Fernandes, Maria I Seixas-Duarte, João B Oliveira-Filho, Alberto J Silva Duarte
The thymus is the site of T cell maturation. Notch receptors (Notch1-4) and ligands (DLL1-3 and Jagged1-2) constitute one of several pathways involved in this process. Our data revealed differential constitutive expression of Notch genes and ligands in T lymphocytes and thymic dendritic cells (tDCs), suggesting their participation in human thymocyte maturation. nTreg analyses indicated that the Notch components function in parallel to promote maturation in the thymus.
2016: Results in Immunology
Ludovic Belle, Kimberle Agle, Vivian Zhou, Cheng Yin-Yuan, Richard Komorowski, Daniel Eastwood, Brent Logan, Jie Sun, Nico Ghilardi, Daniel Cua, Calvin B Williams, Melanie Gaignage, Reece Marillier, Jacques van Snick, William R Drobyski
Re-establishment of competent regulatory pathways has emerged as a strategy to reduce the severity of graft versus host disease (GVHD), and re-calibrate the effector and regulatory arms of the immune system. However, clinically feasible, cost effective strategies that do not require extensive ex vivo cellular manipulation have remained elusive. In the current study, we demonstrate that inhibition of the interleukin 27p28 (IL-27p28) signaling pathway through antibody blockade or genetic ablation prevented lethal GVHD in multiple murine transplant models...
August 3, 2016: Blood
Makoto Miyara, Driss Chader, Aude Burlion, Jérémie Goldstein, Delphine Sterlin, Françoise Norol, Hélène Trebeden-Nègre, Laetitia Claër, Shimon Sakaguchi, Gilles Marodon, Zahir Amoura, Guy Gorochov
FOXP3+ regulatory T cell (Treg) based cellular therapies represent promising therapeutic options in autoimmunity, allergy, transplantation and prevention of Graft Versus Host (GVH) Disease. Among human FOXP3-expressing CD4+T cells, only the CD45RA+ naïve Treg (nTreg) subset is suitable for in vitro expansion. However, FOXP3 expression decays in cells using currently described culture protocols. Rapamycin alone was not able to prevent FOXP3 loss in nTregs cells, as only a half of them maintained FOXP3 expression after 14 days of culture...
July 28, 2016: Oncotarget
Jessica Heinrichs, Jun Li, Hung Nguyen, Yongxia Wu, David Bastian, Anusara Daethanasanmak, M-Hanief Sofi, Steven Schutt, Chen Liu, Junfei Jin, Brian Betts, Claudio Anasetti, Xue-Zhong Yu
Adoptive natural regulatory T cell (nTreg) therapy has improved the outcome for patients suffering from graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (Allo-HCT). However, fear of broad immune suppression and subsequent dampening of beneficial graft-versus-leukemia (GVL) responses remains a challenge. To address this concern, we generated alloreactive induced Tregs (iTregs) from resting CD4(+) or CD8(+) T cells and tested their ability to suppress GVH and maintain GVL responses...
June 2016: Oncoimmunology
Maryam Azimi, Saeed Aslani, Sahar Mortezagholi, Amir Salek, Mohammad Reza Javan, Alireza Rezaiemanesh, Mojgan Ghaedi, Mehrdad Gholamzad, Eisa Salehi
Two categories of regulatory T cells (Tregs), nTreg and iTreg, play vital roles in orchestrating the integrity of a host in the course of an immune response. Tregs commonly belong to CD4+ CD25+ T cells and they are characterized by a transcription factor - forkhead box P3 (FoxP3). Within the space of the last few years, interests have been drawn to Tregs as a therapeutic tool in several settings like autoimmune disease, transplantation, and tumor disorders. As a consequence, to assess the functional properties of Tregs, namely through their ability to suppress other cells, cytokine expression, and proliferation in a variety of conditions, it is mandatory to gain better approaches to this end...
October 2016: Immunological Investigations
Dipica Haribhai, Talal A Chatila, Calvin B Williams
Regulatory T (Treg) cells that express the transcription factor Foxp3 are essential for maintaining tolerance at mucosal interfaces, where they act by controlling inflammation and promoting epithelial cell homeostasis. There are two major regulatory T-cell subsets, "natural" CD4(+) Treg (nTreg) cells that develop in the thymus and "induced" Treg (iTreg) cells that develop from conventional CD4(+) T (Tconv) cells in the periphery. Dysregulated Treg cell responses are associated with autoimmune diseases, including inflammatory bowel disease (IBD) and arthritis...
2016: Methods in Molecular Biology
Maria Metzker, Maria Shipkova, Nicolas von Ahsen, Rainer Andag, Manabu Abe, Ortrun Canzler, Corinne Klett, Simone Leicht, C Olbricht, Eberhard Wieland
OBJECTIVES: Regulatory T cells (Tregs) which may indicate operational tolerance provide a promising biomarker for individualization of immunosuppression. Naturally thymus-derived Tregs (nTregs) represent the major suppressive phenotype and can be identified by their demethylation status in the Tregs Specific Demethylated Region (TSDR) of the Forkhead-Box-P3 (FOXP3) gene using quantitative PCR (qPCR). DESIGN AND METHODS: The analytical performance of a TSDR demethylation qPCR assay was assessed in whole blood of healthy individuals (HI) and kidney transplant recipients (KTR)...
May 21, 2016: Clinical Biochemistry
David A Clark
Natural Foxp3(+) regulatory T cells (nTregs) defined by expression of the Foxp3 marker generated in the thymus against self autoantigens prevent systemic autoimmune and inflammatory disease. A second population of Tregs induced by exogenous antigens in the periphery (iTregs) are currently thought to play a key role in preventing infertility, recurrent pregnancy loss (occult and clinically-evident), pre-eclampsia, fetal growth restriction, and premature birth in outbred matings where the father is histoincompatible with the mother...
August 2016: Journal of Reproductive Immunology
Jinyu Li, Jinyao Li, Adila Aipire, JiaoJiao Luo, Pengfei Yuan, Fuchun Zhang
Our previous study reported that the combination of Pleurotus ferulae water extract (PFWE) and CpG (PFWE+CpG) enhanced the maturation and function of dendritic cells (DCs). Here, we investigated the effects of PFWE+CpG on the immune responses and antitumor efficacy of DC-based vaccine. We observed that all of HPV E6 and E7 peptides pulsed DCs (HPV-immature DCs, HPV+PFWE-, +CpG- or +PFWE+CpG-DCs) induced antigen-specific CD8(+) T cell responses and HPV+PFWE+CpG-DCs induced highest level of CD8(+) T cell responses...
June 30, 2016: Vaccine
Soheil Tavakolpour, Maryam Daneshpazhooh, Hamid Reza Mahmoudi, Kamran Balighi
The efficient treatment of pemphigus with no certain side effect remained a controversial issue. Although there are various options for controlling disease severity, the majority of them may cause serious side effects. Retinoic acid (RA), an active metabolite converted from vitamin A, plays an active role in immune functions. Effects of RA, especially all-trans-Retinoic Acid (ATRA) on different types of cells involved in immune responses were analyzed in vitro and in vivo. RAs could affect the differentiation of T helper (Th) cells, B cells responses, stabilization of both natural regulatory T cells (nTregs) and regulatory B cells (Bregs) populations, and regulating the expression of critical genes in immune responses...
July 2016: International Immunopharmacology
Ram Sabarish, Suresh Ranga Rao, Vamsi Lavu
INTRODUCTION: The T cells play a central role in the aetiopathogenesis of periodontal disease. Natural T regulatory cells (nTreg) are the key stone immunoregulatory elements having an anergic phenotype and play an important role in the suppression of exaggerated immune responses thereby maintaining homeostasis. There are increasing evidences for the role of nTreg in the periodontal disease pathogenesis. AIM: To identify the proportion of natural T regulatory cells in the peripheral blood of periodontally healthy subjects and subjects with chronic periodontitis...
March 2016: Journal of Clinical and Diagnostic Research: JCDR
Zhe Cai, Chun Kwok Wong, Jie Dong, Delong Jiao, Man Chu, Ping Chung Leung, Clara Bik San Lau, Ching Po Lau, Lai Shan Tam, Christopher Wai Kei Lam
BACKGROUND: Ganoderma lucidum (Lingzhi; LZ) and San-Miao-San (SMS) are Chinese medicines (CMs) used to treat inflammatory ailments and numbing syndrome/arthralgia syndrome (Bi Zheng), respectively. Given that the main symptoms of systemic lupus erythematosus (SLE) include inflammation of the joints, joint pain, edema and palpitations of the heart because of problems associated with Bi Zheng, it was envisaged that LZ and SMS could be used as potential treatments for this autoimmune disease...
2016: Chinese Medicine
Manching Ku, Shih-En Chang, Julio Hernandez, Justin R Abadejos, Mohsen Sabouri-Ghomi, Niklas J Muenchmeier, Anna Schwarz, Anna M Valencia, Oktay Kirak
To study the development and function of "natural-arising" T regulatory (nTreg) cells, we developed a novel nTreg model on pure nonobese diabetic background using epigenetic reprogramming via somatic cell nuclear transfer. On RAG1-deficient background, we found that monoclonal FoxP3(+)CD4(+)Treg cells developed in the thymus in the absence of other T cells. Adoptive transfer experiments revealed that the thymic niche is not a limiting factor in nTreg development. In addition, we showed that the T-cell receptor (TCR) β-chain of our nTreg model was not only sufficient to bias T-cell development toward the CD4 lineage, but we also demonstrated that this TCR β-chain was able to provide stronger TCR signals...
April 19, 2016: Proceedings of the National Academy of Sciences of the United States of America
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