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Neuro-Immune Interactions in Inflammation and Autoimmunity

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455331 Year: Pages: 222 DOI: 10.3389/978-2-88945-533-1 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2019-01-23 14:53:42
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The nervous system plays an important role in the regulation of immunity and inflammation. On the other hand unbalanced immune responses in inflammatory and autoimmune conditions may have a deleterious impact on neuronal integrity and brain function.Recent studies have characterized neural pathways communicating peripheral inflammatory signals to the CNS, and brain- and spinal cord-derived circuitries controlling various innate and adaptive immune responses and inflammation. A prototypical neural reflex circuit that regulates immunity and inflammation is the vagus nerve-based “inflammatory reflex”. Ongoing research has revealed cellular and molecular mechanisms underlying these neural circuits and indicated new therapeutic approaches in inflammatory and autoimmune disorders. Pharmacological and bioelectronic modulation of neural circuitry has been successfully explored in preclinical settings of sepsis, arthritis, inflammatory bowel disease, obesity-driven disorders, diabetes and other diseases. These studies paved the way to successful clinical trials with bioelectronic neuronal modulation in rheumatoid arthritis and inflammatory bowel disease.Dysregulated release of cytokines and other inflammatory molecules may have a severe impact on brain function. Brain inflammation (neuroinflammation), imbalances in brain neuronal integrity and neurotransmitter systems, and cognitive impairment are characteristic features of post-operative conditions, sepsis, liver diseases, diabetes and other disorders characterized by immune and metabolic dysregulation. Derangements in cytokine release also play a pivotal role in depression. Characteristic brain reactive antibodies in autoimmune conditions, including systemic lupus erythematosus and neuromyelitis optica, significantly contribute to brain pathology and cognitive impairment. These studies, and the simultaneous characterization of neuro-protective cytokines, identified new therapeutic approaches for treating neurological complications in inflammatory and autoimmune disorders.This Frontiers Research Topic is a forum for publishing research findings and methodological and conceptual advances at the intersection of immunology and neuroscience. We hope that presenting new insight into bi-directional neuro-immune communication in inflammation and autoimmunity will foster further collaborations and facilitate the development of new efficient therapeutic strategies.

Beyond the borders: The gates and fences of Neuroimmune interaction

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192748 Year: Pages: 119 DOI: 10.3389/978-2-88919-274-8 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2015-12-03 13:02:24
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Neuroimmunology is a rapidly growing emerging field at which two old sciences have converged to integrate two different types of responses into a single coherent response involving the coordinated action of both systems, neural and immune. During long time it was thought that both systems worked separately and in divergent pathways. The brain was considered an immunoprivileged site and the immune organs were deemed as independent of any neural influence and also of nervous innervation. Time has gone and has proven that the borders between both systems were merely artificial. Since the beginning of Neuroimmunology in the 1980s much work has been done to elucidate the gates and fences in neuro-immune interactions. Brain was shown to be under the continuous surveillance of the immune system, even under basal physiological conditions in the absence of any pathology. Likely, it was found a profuse nervous innervation of lymphoid organs and even of single immune cells. Gates for direct neural immune communication were found both centrally and peripherally. Centrally, the gates, but also the fences, were situated at the brain barriers, the blood-brain barrier and the blood-cerebrospinal fluid barrier, and at the circunventricular organs. Peripherally, the fences constituted the apparent diverse nature of molecules involved in neural and immune signaling; however, time proved that both system were capable of producing the same signaling molecules and also systematically responded to the molecules released by the other system. Therefore, the gates were open for direct neural-immune communication at the peripheral level. This Research Topic aimed to include original reports, reviews and technical reports regarding the description of the gates and fences in neural immune interactions. We intended to provide an extensive view of the mechanisms governing central and peripheral neural-immune interactions, and the role of the borders, the blood-neural barriers, in the regulation of the neural-immune communication.

CD4+ T cell differentiation in infection: amendments to the Th1/Th2 axiom

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195657 Year: Pages: 111 DOI: 10.3389/978-2-88919-565-7 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-01-19 14:05:46
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CD4+ T lymphocytes play an essential role in host defense against bacterial, parasitic and viral infections. During infection, under the influence of intrinsic signals received through peptide-MHC/TCR interactions and extrinsic signals provided by pathogen-conditioned dendritic and other accessory cells, CD4+ T cells proliferate and differentiate into specialized T helper (Th) effectors, which produce distinct sets of cytokines tailored to combat a specific class of microbes. The concept of CD4+ T cell multi-functionality was developed after the seminal discovery of Th1 and Th2 cells nearly 30 years ago. Although the Th1/Th2 paradigm has successfully withstood the test of time, in the past decade additional Th subsets (Th17, Tfh, Th22, Th9) have been identified. Similarly, single cell analyses of cytokines and master transcriptional factors have revealed that, at the population level, CD4+ T cell responses are far more heterogeneous than initially anticipated. While some of the checkpoints in Th cell specification have been identified, recent studies of transcriptional and epigenetic regulation have uncovered a significant flexibility during the course CD4+ T lymphocyte polarization. In addition, Th cells expressing cytokines with counteracting functions, as a measure of self-regulation, display yet another level of diversity. Understanding the mechanisms that control the balance between stability vs. plasticity of Th effectors both at the time of initiation of immune response and during development of CD4 T cell memory is critical for the rational design of better vaccines and new immunotherapeutic strategies. This research topic will cover current views on Th cell development, with a focus on the mechanisms that govern differentiation, function and regulation of effector Th cells in the context of microbial infections.

NK Cell-Based Cancer Immunotherapy

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199341 Year: Pages: 222 DOI: 10.3389/978-2-88919-934-1 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2016-01-19 14:05:46
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Natural killer (NK) cells are innate lymphoid cells that have a significant role in regulating the defenses against cancer development and certain viral infections. They are equipped with an array of activating and inhibitory receptors that stimulate or diminish NK cell activity, respectively. Inhibitory receptors include, among others, the MHC class I ligands killer cell immunoglobulin-like receptors (KIR) in humans, and members of the Ly49 family of receptors in mice, and CD94/NKG2A. Activating receptors include cytokine and chemokine receptors, and those that interact with ligands expressed on target cells, such as the natural cytotoxicity receptors or NCRs (NKp30, NKp44 and NKp46), NKG2D, CD244 and DNAM-1. In addition, NK cells express Fc?RIIIA or CD16, the receptor that exerts antibody-dependent cell mediated cytotoxicity (ADCC). NK cells also express the death ligands FasL and TRAIL. The killing or sparing of target cells depends on the integration of distinct signals that originate from NK cell receptors. NK cells spare healthy cells that express normal levels of MHC class I molecules and low amounts of stress-induced self-molecules, whereas they kill target cells that down-regulate MHC class I molecules and/or up-regulate stress-induced self-molecules. The latter are common signatures of virus-infected cells and tumors. All the accumulated knowledge on NK cell biology, along with many clinical observations, is driving multiple efforts to improve the arsenal of NK cell-based therapeutic tools in the fight against malignant diseases. Indeed, NK cell-based immunotherapy is becoming a promising approach for the treatment of many cancers. It is well known that NK cells have a significant role in the anti-tumor effect of therapeutic antibodies that use ADCC as a mechanism of action. In addition to this, administration of autologous and allogeneic NK cells after activation and expansion ex vivo is used in the treatment of cancer. Moreover, adoptive transfer of NK cell lines has been tested in humans, and genetically modified NK cells expressing chimeric antigen receptors are being studied in preclinical models for potential use in the clinic.

Mechanisms of neuroinflammation and inflammatory neurodegeneration in acute brain injury

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196913 Year: Pages: 284 DOI: 10.3389/978-2-88919-691-3 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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Mechanisms of brain-immune interactions became a cutting-edge topic in systemic neurosciences over the past years. Acute lesions of the brain parenchyma, particularly, induce a profound and highly complex neuroinflammatory reaction with similar mechanistic properties between differing disease paradigms like ischemic stroke, intracerebral hemorrhage (ICH) and traumatic brain injury (TBI). Resident microglial cells sense tissue damage and initiate inflammation, activation of the endothelial brain-immune interface promotes recruitment of systemic immune cells to the brain and systemic humoral immune mediators (e.g. complements and cytokines) enter the brain through the damaged blood-brain barrier. These cellular and humoral constituents of the neuroinflammatory reaction to brain injury contribute substantially to secondary brain damage and neurodegeneration. Diverse inflammatory cascades such as pro-inflammatory cytokine secretion of invading leukocytes and direct cell-cell-contact cytotoxicity between lymphocytes and neurons have been demonstrated to mediate the inflammatory ‘collateral damage’ in models of acute brain injury. Besides mediating neuronal cell loss and degeneration, secondary inflammatory mechanisms also contribute to functional modulation of neurons and the impact of post-lesional neuroinflammation can even be detected on the behavioral level. The contribution of several specific immune cell subpopulations to the complex orchestration of secondary neuroinflammation has been revealed just recently. However, the differential vulnerability of specific neuronal cell types and the molecular mechanisms of inflammatory neurodegeneration are still elusive. Furthermore, we are only on the verge of characterizing the control of long-term recovery and neuronal plasticity after brain damage by inflammatory pathways. Yet, a more detailed but also comprehensive understanding of the multifaceted interaction of these two supersystems is of direct translational relevance. Immunotherapeutic strategies currently shift to the center of translational research in acute CNS lesion since all clinical trials investigating direct neuroprotective therapies failed. To advance our knowledge on brain-immune communications after brain damage an interdisciplinary approach covered by cellular neuroscience as well as neuroimmunology, brain imaging and behavioral sciences is crucial to thoroughly depict the intricate mechanisms.

The Schistosomiasis Vaccine - It Is Time to Stand Up

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197415 Year: Pages: 82 DOI: 10.3389/978-2-88919-741-5 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-04-07 11:22:02
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Schistosomiasis is a severe parasitic disease, endemic in 74 developing countries with up to 600 million people, including many children, infected and 800 million at risk of contracting the disease following infection with Schistosoma mansoni, S. haematobium or S. japonicum. Disease burden is estimated to exceed 70 million disability-adjusted life-years, and leads to remarkably high YLD (years lived with disability) rates. Even more importantly, people with schistosomiasis are highly susceptible to malaria, tuberculosis and hepatic and acquired immunodeficiency viruses. There is only one drug, praziquantel, currently available for treatment and it has high efficacy, low cost, and limited side effects. However, only 13% of the target population has received the drug, and those treated are at continuous risk of reinfection necessitating repeated drug administration and the emergence of drug resistant parasites is a constant threat. There currently is no vaccine. While the target of >40% protection has been achieved with some molecules such as excretory-secretory proteins including calpain, glyceraldehyde 3-phosphate dehydrogenase, and cysteine peptidases, very recent articles reiterate the findings published during the last 2 decades of the last century, contradicting the established data of the pioneers of schistosome biology. A consensus should be reached without delay, in order to propose collaborative independent experiments and proceed ahead to pre- and clinical trials with efficacious candidate vaccine molecules. The proposed plan aims to finally reach an objective and fruitful agreement , via inviting established and young researchers from the United States, Brazil, China, Australia, and Europe who are working with different vaccine antigens, adjuvants, and approaches for immunization against S. mansoni, S. haematobium, and S. japonicum. It is hoped that the forum will end with a very few candidate antigens and a consensus approach regarding target immune responses, thus leading to encouraging the World Health Organization and other international foundations to sponsor the development and implementation of the urgently required, yet still elusive, vaccine for preventing and eliminating the transmission of schistosomiasis.

Bone Marrow T Cells at the Center Stage in Immunological Memory

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450930 Year: Pages: 84 DOI: 10.3389/978-2-88945-093-0 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2017-07-06 13:27:36
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Increasing evidence supports the notion that bone marrow (BM) represents a relevant player in T cell responses, particularly in its role as a specialized organ for long-term memory. Memory T cells are enriched in the BM over long times after priming, and can be recruited to the periphery upon antigenic challenge. The articles in this research topic include discussions of whether these T cells are passing-through or truly resident, as well as a debate on the extent of proliferation of BM memory T cells. Original research articles in this collection include an analysis of the number of memory T cells found in different bones as well as effects of B cell depletion on T cell memory in the BM. T cells in the BM can influence a number of processes, from bone remodeling, control of cancer, to effects on hemopoiesis or Graft versus Host Disease (GVHD). This research topic contains several contributions to these topics including discussions on how to translate BM T cell knowledge into medicine.

Therapeutic Strategies to Spinal Cord Injury

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ISBN: 9783038974062 9783038974079 Year: Pages: 238 DOI: 10.3390/books978-3-03897-407-9 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General) --- Therapeutics
Added to DOAB on : 2018-12-12 10:33:09
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ca. 200 words; this text will present the book in all promotional forms (e.g. flyers). Please describe the book in straightforward and consumer-friendly terms.This Special Issue gathers eight research articles covering a broad range of strategies on how to combat spinal cord injuries, from searching for therapeutic target molecules, tackling inflammatory reactions, utilizing cell therapy or cell-based products, combined strategies for axonal plasticity assessment, and prevention of post-surgical epidural adhesions. Moreover, four reviews cover recent findings about the role of stress-activated protein kinases in SCI; progress in stem cell therapies; the mechanisms and benefits of activity-based physical rehabilitation therapies with adjuvant testosterone; and, finally, translational regenerative therapies for chronic spinal cord injury.

Second hand smoke and COPD: lessons from animal studies

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193165 Year: Pages: 91 DOI: 10.3389/978-2-88919-316-5 Language: English
Publisher: Frontiers Media SA
Subject: Physiology --- Science (General)
Added to DOAB on : 2016-02-05 17:24:33
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Cigarette smoke exposure is the key initiator of chronic inflammation, alveolar destruction, and the loss of alveolar blood vessels that lead to the development of chronic obstructive pulmonary disease (COPD) which is comprised of emphysema and chronic bronchitis. Exposure to secondhand smoke (SHS) is the major risk factor for non-smokers to develop emphysema. While the first-hand smoke is directly inhaled by smokers, passive smoking occurs when non-smokers are involuntary exposed to environmental tobacco smoke also known as second hand smoke (SHS). SHS is a mixture of 2 forms of smoke that come from burning tobacco: side stream smoke (smoke that comes from the end of a lit cigarette, pipe, or cigar) and mainstream smoke (smoke that is exhaled by a smoker). These two types of smoke have basically the same composition, however in SHS many toxic components are more concentrated than in first-hand smoke, therefore more hazardous for people’s health. Several pathological events have been implicated in the development of SHS-induced COPD, but many aspects of this pathology remain poorly understood halting the development of new advanced treatments for this detrimental disease. In this respect we have welcomed leading investigators in the field to share their research findings and provide their thoughts regarding the mechanisms of the SHS exposure-induced immune responses and inflammatory mechanisms of lung destruction in SHS-induced COPD and related comorbidities.

Making Science Fun - A Tribute to Our Colleague and Friend, Prof. Antonius G. Rolink (1953-2017)

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889457519 Year: Pages: 211 DOI: 10.3389/978-2-88945-751-9 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2019-01-23 14:53:43
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This Research Topic honors the memory of Prof. Antonius “Ton” G. Rolink (April 19, 1953–August 06, 2017), our colleague, mentor and friend in immunology. It is now over a year since Ton left us. This article collection, authored by many of Ton’s friends and colleagues, reflects the huge contribution to cellular and molecular immunology that work emanating directly from Ton’s own hands and laboratory have made to the understanding of lymphocyte development. Ton’s hard work, expertise, generosity, passion for science and infectious humor were legendary and for all of those lucky enough to have been his colleague, he ensured that science was fun. We take this opportunity of thanking all contributors for submitting their manuscripts; we are sure that Ton would have enjoyed reading and making his own insightful comments on them. In the form of original research and review articles, these papers cover many of Ton’s scientific interests in different aspects of lymphocyte development in mouse and man. In the first section, Development of hematopoietic cells and lymphocytes, Klein et al. describe the accumulation of multipotent hematopoietic progenitors in peripheral lymphoid organs of IL-7xFlt3L double transgenic mice and Pang et al. the role of the transcription factor PU.1 on the development of Common Lymphoid Progenitors. In Early B cell development, Winkler and Mårtensson review the role of the Pre-B cell receptor in B cell development and papers by Hobeika et al. and Brennecke et al. describe models of inducible B cell development. For B cell selection, survival and tolerance, Smulski and Eibel review the role of BAFF and Kowalczyk-Quintans et al. analyse the role of membrane-bound BAFF. The impact of BIM on B cell homeostasis is discussed by Liu et al. The role of the MEK-ERK pathway in B cell tolerance is discussed by Greaves et al. and the transcriptional regulation of germinal center development is reviewed by Song and Matthias. For Hematological diseases, Ghia reviews how studies of B cell development help the understanding of Leukemia development, Kim and Schaniel review how iPS technology helps the understanding of hematological diseases and Hellmann et al. describe development of new therapeutic antibody drug conjugates. Finally, in T cell development, homeostasis and graft vs. host disease, Heiler et al. describe the therapeutic effects of IL-2/anti-IL-2 immune complexes in GvHD, Calvo-Asensio et al. describe the DNA damage response of thymocyte progenitors and Mori and Pieters review the role of Coronin 1 in T cell survival.

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