Download or read book Tolerogenic Dendritic Cells and Regulatory T Cells as Therapeutics for Immune Mediated Disorders written by Djordje Miljkovic and published by Frontiers Media SA. This book was released on 2021-11-16 with total page 411 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Emerging Therapeutics for Immune Tolerance written by Hyewon Phee and published by Frontiers Media SA. This book was released on 2021-11-30 with total page 327 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Regulatory T Cells in Inflammation written by Leonie S. Taams and published by Springer Science & Business Media. This book was released on 2006-03-30 with total page 242 pages. Available in PDF, EPUB and Kindle. Book excerpt: Regulatory T-cells are essential components of the immune system, and several different subsets of regulatory T-cells have been described. Considerable regulatory function has been attributed to the CD4+CD25+ T-cell subset. These cells act by suppressing adaptive and possibly innate immune responses thereby maintaining or restoring the balance between immunity and tolerance. The suppressive effects of CD4+CD25+ regulatory T-cells are cell-contact dependent. Recent developments and viewpoints in the field of CD4+CD25+ regulatory T-cells as well as the potential use of regulatory T-cells in immunotherapy of inflammatory diseases are discussed in this volume. By linking data from experimental models with recent findings from the clinic, this book will be of interest to immunologists and other biomedical researchers as well as clinicians interested in the regulation and manipulation of the immune response during inflammatory disease.
Download or read book Molecular Mechanisms of Dendritic Cell Mediated Immune Tolerance and Autoimmunity written by Fang Zhou and published by Frontiers Media SA. This book was released on 2024-04-09 with total page 213 pages. Available in PDF, EPUB and Kindle. Book excerpt: Dendritic cells (DCs) play a critical role in immune system, as they are necessary both for innate and adaptive immunity. According to their function, dendritic cells can be classified in immune tolerogenic or inflammatory DCs. DCs have been shown to regulate T cell-mediated immune responses and lead to immune tolerance and autoimmunity. For example, immune-tolerogenic DCs facilitate the development of regulatory T cells and inhibit T helper 17-mediated autoimmunity in mice with experimental autoimmune encephalomyelitis. Moreover, inflammatory DCs activate CD8+ and CD4+ T cells and elicit T cell-mediated inflammatory immune responses in vivo. However, the molecular and cellular mechanisms underlying DC-mediated immune tolerance and autoimmunity are still obscure.
Download or read book Tolerogenic Dendritic Cells for Therapy of Immune Mediated Inflammatory Diseases written by Urban Švajger and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Tolerogenic Dendritic Cells for Therapy of Immune-Mediated Inflammatory Diseases.
Download or read book CD4 CD25 Regulatory T Cells Origin Function and Therapeutic Potential written by B. Kyewski and published by Springer Science & Business Media. This book was released on 2006-01-09 with total page 331 pages. Available in PDF, EPUB and Kindle. Book excerpt: The vertebrate immune system defends the organism against invading pathogens while at the same time being self-tolerant to the body’s own constituents thus preserving its integrity. Multiple mechanisms work in concert to ensure self-tolerance. Apart from purging the T cell repertoire from auto-reactive T cells via negative selection in the thymus dominant tolerance exerted by regulatory T cells plays a major role in tolerance imposition and maintenance. Among the various regulatory/suppressive cells hitherto described, CD4+CD25+ regulatory T cells (Treg) and interleukin-10 producing T regulatory 1 (Tr1) cells have been studied in most detail and are the subject of most articles in this issue. Treg, also called "natural" regulatory T cells, will be traced from their intra-thymic origin to the site of their action in peripheral lymphoid organs and tissues. The repertoire of Treg is clearly biased towards recognition of self-antigens, thereby potentially preventing autoimmune diseases such as gastritis and oophoritis. Regulatory T cells, however also control infections, allergies and tolerance to transplanted tissues and this requires their induction in the periphery under conditions which are not yet fully understood. The concept of dominant tolerance, by far not novel, will offer new insights and hopefully tools for the successful treatment of autoimmune diseases, improved cancer immunotherapy and transplant survival. The fulfillment of these high expectations will, however, require their unambiguous identification and a better understanding of their mode of action.
Download or read book Dendritic Cell Control of Immune Responses written by Penelope Anne Morel and published by Frontiers Media SA. This book was released on 2016-07-27 with total page 123 pages. Available in PDF, EPUB and Kindle. Book excerpt: Dendritic cells (DC) are among the first cells to encounter pathogens and damage in peripheral tissues and, upon activation, DC migrate to lymph nodes where they activate and educate T cells to initiate and shape the immune response. DC present pathogen-derived antigen to T cells and drive T cell differentiation into particular effector cells through the expression and secretion of co-stimulatory molecules and cytokines respectively. The study of DC biology has included the identification of multiple DC subsets in tissues and lymphoid organs, the differentiation and plasticity of DC subsets, the functional consequences of DC interaction with pathogen, control of DC migratory properties and the impact of DC on T cell activation and differentiation. In recent years sophisticated systems biology approaches have been developed to deepen our understanding of DC function. These studies have identified differences between DC subsets located in various tissues and critical factors that drive the outcome of the interaction between DC and T cells. DC are currently being used in in various clinical therapeutic settings, including as vaccines for cancer and autoimmune disease. A clear understanding of DC factors that contribute to specific immune responses is vital to the success of DC based therapies. This research topic will give a comprehensive overview of current issues in DC biology and provides an update on the clinical uses of DC in the therapy of autoimmunity and cancer.
Download or read book The nature of activatory and tolerogenic dendritic cell derived signal 2 written by Francesca Granucci and published by Frontiers E-books. This book was released on 2014-07-08 with total page 153 pages. Available in PDF, EPUB and Kindle. Book excerpt: One of the most interesting issues in immunology is how the innate and adaptive branches of the immune system cooperate in vertebrate organisms to respond and destroy invading microorganisms without destroying self-tissues. More than 20 years ago, Charles Janeway proposed the innate immune recognition theory [1]. He hypothesized the existence of innate receptors (Pattern recognition receptors, PRRs) that, by recognizing molecular structures associated to pathogens (PAMPs) and being expressed by antigen presenting cells (APCs) and epithelial cells, could alert the immune system to the presence of a pathogen, making it possible to mount an immediate inflammatory response. Moreover, by transducing the alert signal in professional APCs and inducing the expression of costimulatory molecules, these receptors could control the activation of lymphocytes bearing clonal antigen-specific receptors, thereby promoting appropriate adaptive immune responses. Since adaptive immunity can be activated also following sterile inflammatory conditions, it was subsequently proposed by Polly Matzinger that the innate immune system could be also activated by endogenous danger signals, generically called danger associated molecular patterns (DAMPs)[2]. The first prediction has been amply confirmed by the discovery of Toll-like receptors [3; 4; 5] and cytoplasmic PRRs such as RIG-like receptors [6]. Other PRR families such as the NOD-like receptors and C-type lectins exert immunogenic or tolerogenic signals [7; 8; 9] and may recognize not strictly pathogens but also endogenous danger signals that may lead to inflammasome activation [10; 11] . Dendritic cells (DCs) have been identified as the cells of the innate immune system that, by sensing PAMPs or DAMPs transduce signals to the nucleus. This leads to a transcriptional reprogramming of DCs with the consequent expression of three signals, namely signal 1 (MHC+peptide), signal 2 (surface costimulatory molecules) and signal 3 (cytokines) necessary for the priming of antigen-specific naïve T cell responses (signal 1 and 2) and T cell polarization (signal 3). The reason why DCs are superior with respect to other professional APCs in naïve T cell activation has not been unequivocally defined but in vivo may mainly result from their migration capacity to secondary lymphoid organs. It has not been established whether DCs can provide a special “signal 2” or simply very high levels, compared with other APCs, of commonly expressed signals 1 and 2, so that a naïve T cell could reach the threshold of activation. A second aspect of DC biology needs also to be taken into account. Concerning the question of how self-tissues are not destroyed following the initiation of adaptive immune responses, different mechanisms of central and peripheral auto-reactive T cell tolerization have been proposed [12]. In particular, it has been defined that high affinity T cells are deleted in the thymus, while low affinity auto-reactive T cells or T cells specific for tissue-sequestered antigens that do not have access to the thymus are controlled in the periphery. In a simplified vision of how peripheral T cell tolerance could be induced and maintained, it was thought that, in resting conditions, immature DCs, expressing low levels of signal 1 and low or no levels of signal 2, were able to induce T cell unresponsiveness. Nevertheless, it is now clear that a fundamental contribution to the peripheral tolerance is due to the conversion of naïve T cells into peripheral regulatory T cells (pTreg cells) and it is also clear that DCs need to receive a specific conditioning to become able to induce pTreg cell differentiation. Even more intriguing is that also DCs activated through PRRs, with particular Toll like receptor (TLR) agonists, are capable of generating pTreg cell conversion if these agonists induce the production of the appropriate cytokines.
Download or read book Tolerogenic Antigen Presenting Cells Modulating Unwanted Immune Response at Their Core written by John Isaacs and published by Frontiers Media SA. This book was released on 2019-12-27 with total page 310 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Induction of immune tolerance Addressing unmet medical need in immune mediated diseases and immune responses to biologics written by Amy Rosenberg and published by Frontiers Media SA. This book was released on 2023-09-25 with total page 190 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book TLR 4 Agonism Induces CD25 MHCIIhigh Dendritic Cells in Association with Tolerogenic Antigen Recognition written by Alexander Gevelinger Bastian and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Autoimmune disease is a result of the breakdown in immunological self-tolerance leading to destruction of self-tissues mediated by the aberrant immune attack. In Multiple Sclerosis (MS), CD4+ T cells mediate destruction of myelin in the central nervous system (CNS) leading to debilitating symptoms in afflicted individuals. MS is the leading cause of non-injury disability in young adults, impacting nearly 1 million people in the United States alone. As is the case for many autoimmune diseases, there is no cure for MS, highlighting the urgent need for new therapeutic platforms. A therapeutic approach to reestablish self-tolerance is likely to be more effective and have less side effects than current treatments, highlighting the importance for developing such an approach. At the center of this approach lies CD4+ FOXP3+regulatory T cells (Tregs), which are a subset of T cells that suppress the immune system and play an integral role in controlling autoimmunity. Therapies aimed at increasing Tregs, especially in a disease targeted manner, have the potential to reestablish self-tolerance and cure autoimmunity.All T cells, including Tregs, must recognize antigen on antigen presenting cells (APCs) to perform effector functions. Therefore, targeting an APC niche that supports the development of Tregs is an effective approach for development of autoimmune therapeutics. Dendritic cells (DCs) are a class of APCs known to support Treg development and function. In this study, we show that agonism of Toll-like receptor 4 (TLR-4) with lipopolysaccharide (LPS) or monophosphoryl Lipid A (MPLA) on DCs leads to a CD25+ MHCIIhigh DC phenotype. We show that the expression of CD25 is unique to DCs and that it binds IL-2 from the environment without detectable downstream signaling. Importantly, we show that this bound IL-2 can be utilized by responder T cells, highlighting a potential function of CD25 on DCs. We then combined TLR-4 agonism with our lab's DC-targeting tolerogenic vaccine, GMCSF-MOG, which we have previously shown leads to high levels of Tregs and amelioration of experimental autoimmune encephalomyelitis (EAE) in mice. When GMCSF-MOG is combined with MPLA, Treg levels are increased and extend out to 78 days post injection. The enhanced and extended Treg levels observed when MPLA is included in the vaccine likely play a role in accelerating the GMCSF-MOG-mediated amelioration of EAE and preventing observed EAE relapse. At the crux of DC-mediated tolerance induction is the efficiency of the antigen recognition event. Lower affinity TCR ligation supports tolerance through lower induction of costimulatory molecules (CD40L) and increased induction of inhibitory molecules (PD-1). Furthermore, inhibiting the CD40L/CD40 axis increases Treg induction. Overall, we show that TLR-4 agonism leads to CD25+ MHCIIhigh DCs and functions as a tolerogenic adjuvant when combined with the DC targeting GMSCF-MOG vaccine through support of low-efficiency Treg-favorable antigen recognition events.
Download or read book The Immune Synapse as a Novel Target for Therapy written by Luis Graca and published by Springer Science & Business Media. This book was released on 2007-12-18 with total page 201 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume gives an overview on the progress in immune synapse research, from basic science to clinical trials, and the major mechanisms involved. It discusses how interfering with T cell activation may lead to immune tolerance, immune modulation, and the recruitment of regulatory T cells; the role of monoclonal antibodies in tolerance induction; and mechanisms maintaining dominant tolerance.
Download or read book Dendritic Cells written by Giovanna Lombardi and published by Springer Science & Business Media. This book was released on 2008-11-24 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt: The understanding of the role of dendritic cells (DCs) in immune responses has come a long way since Steinmann and colleagues described these cells in 1972. - tensive research during the intervening period has provided a good understanding of the complexity of the DC system and its pivotal role in immunity. It is also now clearer how different subsets of DCs interact and regulate each other and how DC populations affect the function of other cells of the immune system. The improved understanding of their role in immune response has led to the idea that modulation of DC functions by, for example, pharmacological agents could be used as a pot- tial therapeutic approach in some pathological conditions. The actual applicability and therapeutic potential of all these approaches is yet to be fully demonstrated but nonetheless, animal models of human diseases are proving to be very helpful in the evaluation of manipulated DCs as a new treatment in diseases like cancer, auto- munity or asthma. DCs are integral to the initiation and regulation of immune response (Banchereau et al. 2000). The outcome of antigen presentation by DCs is determined by their maturation status, which can be induced by their interaction with danger signals. To recognise a wide array of pathogen-associated molecular patterns (PAMP), DCs express a number of pattern recognition receptors (PRR) such as Toll-like rec- tors (TLRs) and C-type lectin receptors (CLR) that recognise structural components of pathogens and discriminate between self and non-self molecules.
Download or read book Immune Regulation written by Marc Feldmann and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 384 pages. Available in PDF, EPUB and Kindle. Book excerpt: Leukocyte culture conferences have a long pedigree. This volume records some of the scientific highlights of the 16th such annual con ference, and is a witness to the continuing evolution and popularity of leukocyte culture and of immunology. There is strong evidence of the widening horizons of immunology, both technically, with the obviously major impact of molecular biology into our understanding of cellular processes, and also conceptually. Traditionally, the 'proceedings' of these conferences have been published. But have the books produced really recorded the major part of the conference, the informal, friendly, but intense and some times heated exchanges that take place between workers in tackling very similar problems and systems and which are at the heart of every successful conference? Unfortunately this essence cannot be incorpo rated by soliciting manuscripts. For this reason, we have changed the format of publication, retaining published versions of the symposium papers, but requesting the workshop chairmen to produce a summary of the major new observations and areas of controversy highlighted in their sessions, as a vehicle for defining current areas of interest and debate. Not an easy task, as the workshop topics were culled from the abstracts submitted by the participants, rather than being on predefined topics. The unseasonal warmth in Cambridge was reflected in the atmos phere of the conference, the organization of which benefited from the administrative skills of Jean Bacon, Philippa Wells, Mr. Peter Irving, and Mrs.
Download or read book Gene Therapy of Autoimmune Disease written by Gerald J. Prud'homme and published by Springer. This book was released on 2005-07-13 with total page 149 pages. Available in PDF, EPUB and Kindle. Book excerpt: Autoimmune diseases are diverse and responsible for considerable morbidity. Their etiology remains largely unknown, and current therapy with anti-inflammatory drugs is prone to adverse effects, and rarely curative. New therapies with anti-cytokine antibodies or receptors are promising, but require frequent administration of expensive protein drugs. Gene Therapy of Autoimmune Diseases comprehensively reviews research in gene therapy for autoimmune diseases with viral or non-viral vectors. Gene therapy offers the possibility of long-term, continuous delivery of a wide variety of immunosuppressive, anti-inflammatory, or tolerance-inducing agents. Moreover, highly specific genetically modified cells can be produced. This book discusses the most promising avenues in this exciting new field.
Download or read book Balancing Between Immunity and Tolerance written by Nathalie Cools and published by LAP Lambert Academic Publishing. This book was released on 2010 with total page 176 pages. Available in PDF, EPUB and Kindle. Book excerpt: During the past 10 years, important progress has been made in the field of immunology, leading to a better notion of the relationship between the immune system and disease. While new immunotherapeutic efforts pave the way for the treatment of old diseases, understanding the biology, function and mechanisms of immune cell populations is of utmost concern for the development and optimisation of cellular immune therapies for the induction of effective immune responses in cancer and chronic infections on the one hand, and for the induction of T cell tolerance in autoimmune disorders and transplantation on the other hand. With the data presented in this book, we believe to have contributed to the knowledge on the role of immune effector cells, such as dendritic cells, in maintaining the subtle balance between immunity and tolerance. The data presented clearly open up new avenues in order to improve dendritic cell-based immunotherapies for immune stimulation and tolerance and should be especially usefull to professionals in immunology or anyone else interested in cell-based therapies.
Download or read book An Untold Tale of Tolerance written by Noémi Anna Nagy and published by . This book was released on 2024 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chronic inflammatory disorders, including various autoimmune diseases and allergies, put a significant burden on our societies. As these conditions stem from a breach in immune tolerance, immune modulation could provide novel avenues for disease prevention or cure. Dendritic cells (DCs) are specialized immune cells that can effectively induce the development of regulatory T cells (Tregs), critical adaptive immune cells for dampening inflammation. Both active metabolites of vitamin D3 (VD3) and retinoic acid (RA) can induce tolerogenic DCs, subsequently fostering a Treg response in vitro. Nanocarriers, such as liposomes or plant-based bioparticles, can be used to combine VD3 or RA with autoantigens or allergens and target these factors simultaneously to DCs in tissue to achieve disease-specific tolerance in vivo. In this thesis, we embarked upon developing a nanocarrier-based vaccine product for future in vivo modulation of DCs. We established negatively charged liposomes as most suitable for administering adjuvants to DCs. We found that various subsets of DCs treated with VD3 or RA, in soluble or liposome-loaded form, induced the development of CD4+ but also CD8+ Tregs in vitro. Furthermore, we established an activating yet hypo-allergenic effect of peanut allergen-loaded bioparticles on DCs. Finally, we present a randomized controlled phase I clinical trial examining the peripheral immune effect of subcutaneous VD3 administration in birch pollen allergic patients. Thus, this thesis encompasses the first steps toward a putative DC-targeted vaccine treating chronic inflammation.
