Download or read book Mechanisms of Human Innate Lymphoid Cell Development written by Ansel P. Nalin and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Human innate lymphoid cells (ILCs) comprise a diverse population of lymphocytes with various roles in tissue homeostasis, inflammation, host defense, and malignancy. ILCs collectively include the cytotoxic natural killer (NK) cells, which participate in direct lysis of infected or malignant cells, as well as distinct helper ILC populations (ILC1s, ILC2s, and ILC3s), which mediate their immunomodulatory roles via production of cytokines. Many physiologic pathways rely on the effector functions of NK cells and other ILC subsets; yet, the mechanisms that regulate their differentiation and maturation are not fully known. The overall goal of this research is to further characterize the pathways of human ILC development and to identify the mechanisms that regulate the differentiation and function of mature ILC populations. The results of these studies elucidate the roles of signal pathways and cellular interactions in the regulation of ILC biology. Activation of the Notch signaling pathway promoted the differentiation of non-NK helper ILC subsets at specific stages of development. While direct co-culture of ILC precursor cells with stromal feeder cells (and exogenous IL-7) was sufficient for the acquisition of NK cell markers (CD94 and NKG2A), the simultaneous presence of Notch ligand was required for the differentiation of functional ILC2s and ILC3s under these conditions. Although Notch was not required for NK cell differentiation, it did have an impact on the phenotype of in vitro-derived NK cells. Activation of Notch in the presence of stromal cells promoted the expression of the activating receptor NKp80, suggesting a role for Notch in the later stages of NK cell maturation. Based on the expression patterns of individual Notch receptors, it was hypothesized that there are stage-specific differences in the signaling mechanism. In support of this, it was shown that both NOTCH1 and NOTCH2 were involved in ILC2 and ILC3 differentiation from ILC precursor cells. Alternatively, NOTCH1 was the primary receptor involved in NKp80 acquisition from immature NK cells. It was also determined that the developmental potential for ILC2s, followed by ILC3s, was lost at successive stages of NK cell development. Compared to functional NK cells (those that express NKp80), earlier stages of immature NK cells and ILC precursor cells display greater developmental plasticity and heterogeneity at the bulk population level. It was observed that intermediate ILC populations were highly enriched for expression of CD200R1. Interestingly, the expression (or lack) of CD200R1 in specific populations correlated with significant differences in NK cell phenotypic and functional maturity. An intermediate NK cell subset lacking CD200R1 expression was found to have greater expression of markers associated with mature NK cells despite lacking other typical markers of terminal NK cell maturation, NKp80 and CD16. The phenotypic and functional properties associated with this population suggest that this minor subset of CD200R1- cells is out of sequence with the typical stages of NK cell maturation, further illustrating the heterogeneity of NK/ILC developmental intermediate populations. It was further hypothesized that the biology of mature ILC populations is regulated by tissue-specific interactions in the microenvironment. The NF-kB signaling pathway was identified as a regulator of ILC3 biology. Inhibition of NF-kB signaling resulted in decreased IL-22 production from ILC3s in the presence of IL-18. Likewise, mutation of specific NF-kB binding sites within the IL22 promoter led to decreased transcription. Because IL-18 can activate NF-kB, a tissue-specific mechanism was proposed based on the proximity of lymphocytes with ILC3-associated markers to IL-18-producing dendritic cells within the interfollicular regions of the tonsil. In additional studies of the tissue-specific mechanisms that regulate ILC biology, a novel ILC1 population was identified in the liver using data from single cell RNA Sequencing. These cells demonstrated ILC1-associated phenotypic and functional features and were distinct from other previously described human ILC1 populations, as well as from liver-resident NK cells. These liver-type ILC1s (ltILC1s) produced IFN-gamma; and expressed T-BET; yet, they did not degranulate, nor express the NK-associated markers NKp80 and EOMES. These results further elucidate the mechanisms regulating human ILC development and function. By characterizing the normal processes of ILC biology, these studies establish a foundation for understanding how these processes can become dysregulated in the setting of disease. It is further hoped that the discoveries related to this work can be applied in translational research efforts that seek to optimize the role of the immune system in clinical therapies.
Download or read book Human Innate Lymphoid Cell Development written by Steven Scoville and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Innate lymphoid cells (ILC) were recently discovered as a novel subset of the immune system. While typical adaptive lymphocytes, such as B and T cells, respond in an antigen specific manner, ILCs are distinct in that they lack the gene-rearrangement events necessary to elicit antigen specific responses. Nonetheless, through their unique functional profile ILCs play a vital role in promoting overall health by eliminating certain types of viruses, bacteria, worms, and even cancer cells. In fact, some evidence suggests that cancer cells actively suppress ILCs. ILCs are divided into four distinct populations known as natural killer (NK) cells, ILC1, ILC2 and ILC3, each displaying unique transcriptional and functional effector profiles. They are also found in many different physiological locations, but they are collectively enriched within secondary lymphoid tissues (SLT), such as tonsils and lymph nodes. However, how and where human ILCs develop is currently not known. We hypothesized that ILCs develop from progenitors found in SLT. Our lab previously showed that a distinct population of CD34(+)CD45RA(+) lymphoid progenitors exists in SLTs. Dissecting these progenitors with respect to surface markers commonly found on mature ILC subsets, we discovered a novel progenitor population, identified as CD34(+)CD45RA(+)ID2(+)CD117(+)IL-1R1(+)ROR¿t(+), that is only found in SLT locations such as human tonsils, lymph nodes, and spleen, but not in non-SLT hematopoietic locations such as peripheral blood, cord blood, thymus, and bone marrow. A hallmark of progenitor differentiation is the distinct loss of multi-lineage potential, thus we performed in vitro differentiation assays to determine the lineage restriction of this novel population. Remarkably, the ID2(+)CD117(+)IL-1R1(+) subset we identified was not capable of developing into T cells or dendritic cells, despite being in conditions that promoted the differentiation of those lineages from other SLT progenitor subsets. However, this population was capable of differentiating into all ILC populations as tested in vitro even at the clonal level. Furthermore, subsequent work has also demonstrated that this cell selectively gives rise only to ILCs in vivo, after injecting these cells into an immunodeficient mouse. In conclusion, we are the first to identify and characterize a progenitor population in humans that is only capable of ILC development and no other lymphocyte lineage. These findings are now being used to help us understand how cancer cells work to suppress the development and function of ILCs to promote disease progression. More importantly, our findings provide new targets that may be helpful in overcoming this effect and may be useful in cancer therapy.
Download or read book Innate Lymphoid Cell Development Migration and Function written by Paula Licona-Limón and published by Frontiers Media SA. This book was released on 2023-10-23 with total page 144 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cell lineages derived from common lymphoid progenitors (CLPs) play a critical role in antigen recognition, acute and long term protection against pathogens, and maintenance of immune homeostasis. CLPs give rise to adaptive immune cells that bear unique antigen receptors and to innate immune cells that perform non-redundant roles, particularly during early effector responses, by facilitating local immunity and shaping the ensuing adaptive response. Recent discoveries indicate that innate lymphoid cells (ILCs) exert essential modulatory effects in normal and pathological responses. Because adaptive and innate lymphoid cells share transcription factors, cytokines, and molecular surface markers, it is essential to dissect the contribution of innate lymphoid cell subsets to immune tolerance, maintenance of tissue homeostasis and during the development of inflammatory responses. In this research topic we will focus on the functional diversity and individual roles that the variety of innate lymphoid cell subsets perform in steady state as well as in different pathological conditions including infection and autoimmunity. This will contribute to the generation of a more comprehensive and integrated view of how these cells interact with the environment, collaborate with other cells and regulate tissue homeostasis and immunity in a context-dependent manner. We welcome Original Research, Review, and Mini-review articles related to, but not limited to the following topics: 1. Innate lymphoid cell development and migration 2. Characterization and identification of signals controlling innate lymphoid differentiation and function 3. Molecular interactions between innate lymphoid cells and other immune and non-immune subsets 4. Role of ILCs in tissue homeostasis 5. Role of ILCs in pathology We acknowledge the initiation and support of this Research Topic by the International Union of Immunological Societies (IUIS). We hereby state publicly that the IUIS has had no editorial input in articles included in this Research Topic, thus ensuring that all aspects of this Research Topic are evaluated objectively, unbiased by any specific policy or opinion of the IUIS.
Download or read book Lymphocyte Updates written by Gheorghita Isvoranu and published by BoD – Books on Demand. This book was released on 2017-07-12 with total page 194 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book represents a synergic effort of an international team of specialists in immunology to expand the scientific achievements in the field of lymphocytes. It offers important and specific updated information to researchers, students, teachers, and medical professionals. Moreover, considering the remarkable dynamics of immunology and immunotherapy, this book "Lymphocyte Updates - Cancer, Autoimmunity, and Infection" aims to represent a significant source of concise scientific data and advancement of knowledge in this field. The chapters offer new insights into the latest scientific progress on lymphocyte roles in protective immunity, as well as their involvement in pathogenesis of various disorders.
Download or read book Cytokine Control of Human Innate Lymphoid Cell Development and Function written by Ai Ing Lim and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Innate lymphoid cells (ILC) represent a novel family of hematopoietic effectors that serve essential roles in early immune response by rapid cytokines production. Three distinct groups of ILC subsets have been described. Group 1 ILC include cytotoxic natural killer (NK) cells and other type-1 cytokines (IFN-? and TNF-?) producing cells that regulated by T-BET. Group 2 ILC (ILC2) express GATA-3 and ROR?, secrete type-2 cytokines, IL-5 and IL-13. Group 3 ILC (ILC3) utilize ROR?t to drive production of the TH17-associated cytokines, IL-17 and/or IL-22. In this thesis, I have performed series of experiments to uncover the developmental pathway and function of human ILC that may allow us to harness ILC in diverse clinical settings. First, I analyzed the phenotypic and functional heterogeneity of human peripheral blood ILC2. I found human IL-13+ ILC2 can acquire the capacity to produce IFN-?, thereby generating ÔplasticÕ ILC2. ILC2 cultures demonstrated that IFN-?+ ILC2 clones could be derived and were stably associated with increased T-BET expression. The inductive mechanism for ILC2 plasticity was mapped to the IL-12/IL-12R signaling pathway and was confirmed through analysis of patients with Mendelian susceptibility to mycobacterial disease (MSMD) due to IL-12R?1 deficiencies that failed to generate plastic ILC2. This IL-13+IFN-?+ ILC2 are detected ex vivo in gut tissues from CrohnÕs patients. Second, I identified and isolated ILC precursors (ILCP) in peripheral blood of healthy donors. This circulating ILCP can give rise to four lineages of mature ILC including cytotoxic NK cells and helper ILC1, 2 and 3 in vitro and in vivo. Transcirptomic and epigenetic analysis showed ILCP have ILC-committed transcription factor profiles but have mature ILC signature locus at the epigenetics poised states. We further identified ILCP in various tissues including fetal liver, cord blood, postnatal lung and tonsil. Our result proposed a new model of ÒILC-poiesisÓ where circulating ILCP serve as cellular substrates to generate mature ILC subsets in tissues. Understanding the role of IL-12 on driving ILC2 to ILC1 plasticity may allow us to target plastic ILC2 in various diseases. The identification and isolation of ILCP from circulating blood allow further transfer into clinical setting for cellular therapy, especially for various diseases that ILC has been shown to be importance including infection, allergy, cancer and metabolic diseases.
Download or read book Janeway s Immunobiology written by Kenneth Murphy and published by Garland Science. This book was released on 2010-06-22 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.
Download or read book Human Innate Lymphoid Cell Biology and Development written by Luxi Chen and published by . This book was released on 2019 with total page 141 pages. Available in PDF, EPUB and Kindle. Book excerpt: Based on these data, we hypothesized that in humans all ILCs share a common developmental pathway in tonsils and that at some point, each ILC subset terminally differentiates along its own developmental trajectory. Here we elucidated key steps of NK cell, ILC2, and ILC3 development within human tonsils using ex vivo molecular, transcriptional, and functional profiling and lineage differentiation assays. We demonstrated that while tonsillar NK cells, ILC2s, and ILC3s originate from a common ILC precursor cell identified as CD34-CD117+, final steps of ILC2 development deviate independently and become mutually exclusive from those of NK cells and ILC3s, whose developmental pathways overlap. Moreover, we discovered a CD34-CD117+ ILC precursor population that expresses CD56 and gives rise to NK cells and ILC3s but not to ILC2s. Collectively, our data support a comprehensive model for human ILC development in tonsils, advancing our understanding of basic ILC biology within the human immune system. Importantly, elucidating these fundamental developmental pathways have enabled us to gain greater insight into how cancer cells can disrupt ILC development and function to further disease progression.
Download or read book Neonatal Hematology written by Pedro A. de Alarcón and published by Cambridge University Press. This book was released on 2021-02-18 with total page 501 pages. Available in PDF, EPUB and Kindle. Book excerpt: An essential guide to the pathogenesis, diagnosis and management of hematologic problems in the neonate, covering erythrocyte disorders, leukocyte disorders, immunologic disorders and hemostatic disorders. Guidance is practical, including blood test interpretation, advice on transfusions and reference ranges for hematological values.
Download or read book Molecular Biology of The Cell written by Bruce Alberts and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Innate Lymphoid Cells written by Xiao-Hong Sun and published by Springer Nature. This book was released on 2022-05-14 with total page 169 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book aims to systemically summarize the key findings about Innate lymphoid cells (ILCs) and present the consensus of current views and prospective. ILCs are a class of newly recognized immune cells which play an instructive role in shaping immunity in physiological and pathological conditions. This book discusses the differentiation of ILC, the relation of ILCs with respiratory function, inflammation in the gut, skin disorders, cancer, neurobiology and microbes. The knowledge included in this book is valuable for both basic immunologists and clinicians in understanding the heterogenetic immune responses in disease and health.
Download or read book Type 2 Immunity written by R. Lee Reinhardt and published by Humana. This book was released on 2018-06-29 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides researchers the opportunity to investigate type-2-associated diseases in their laboratories. Beginning with chapters describing various models of type-2 immunity, the volume then continues by detailing cellular protocols designed to identify, characterize, and assess the function of key adaptive and innate immune cells involved in type-2 inflammation; approaches to isolate and evaluate specific cellular subsets at the genetic, epigenetic, and molecular level; protocols to assess type-2 immunity and its relationship to organismal and metabolic systems (ex. Microbiome). This book concludes with a section that explores the use of primary human cells in evaluating relevance to the clinic. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Vital and authoritative, Type 2 Immunity: Methods and Protocols aims to provide a broad network of methods that can be used to develop a hypothesis and investigate its potential from bench to beside.
Download or read book Inflammation 4 Volume Set written by Jean-Marc Cavaillon and published by John Wiley & Sons. This book was released on 2018-02-20 with total page 1818 pages. Available in PDF, EPUB and Kindle. Book excerpt: Dieses Fachbuch erläutert die molekularen Grundlagen von Entzündungen, spannt den Bogen zu Infektionskrankheiten und den Zusammenhang zwischen Entzündungen und chronischen Erkrankungen, behandelt abschließend den Heilungsprozess und zeigt Therapiemöglichkeiten.
Download or read book Innate Immunity Resistance and Disease Promoting Principles written by G. Hartmann and published by Karger Medical and Scientific Publishers. This book was released on 2013-06-05 with total page 140 pages. Available in PDF, EPUB and Kindle. Book excerpt: Our understanding of the complex innate immune response is increasing rapidly. Its role in the protection against viral or bacterial pathogens is essential for the survival of an organism. However, it is equally important to avoid unregulated inflammation because innate immune responses can cause or promote chronic autoinflammatory diseases such as gout, atherosclerosis, type 2 diabetes or certain aspects of the metabolic syndrome. In this book leading international experts in the field of innate immunity share their findings, define the ‚state of the art‘ in this field and evaluate how insight into the molecular basis of these diseases could help in the design of new therapies. A tremendous amount of work on the innate immune response has been done over the last fifteen years, culminating in the 2011 Nobel Prize in Physiology/Medicine awarded for the discoveries of Toll genes in immunity in flies, membrane-bound Toll-like receptors in mammals, and dendritic cells as initiators of adaptive immunity.
Download or read book Differentiation and Mechanisms of Activation of Innate Lymphoid Cells written by Marina Cella and published by Frontiers Media SA. This book was released on 2019-08-12 with total page 129 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Oxford Textbook of Rheumatology written by Philip Conaghan and published by Oxford University Press. This book was released on 2013-10 with total page 1553 pages. Available in PDF, EPUB and Kindle. Book excerpt: A strong clinical emphasis is present throughout this volume from the first section of commonly presenting problems through to the section addressing problems shared with a range of other clinical sub-specialties.
Download or read book The Impact of Food Bioactives on Health written by Kitty Verhoeckx and published by Springer. This book was released on 2015-04-29 with total page 341 pages. Available in PDF, EPUB and Kindle. Book excerpt: “Infogest” (Improving Health Properties of Food by Sharing our Knowledge on the Digestive Process) is an EU COST action/network in the domain of Food and Agriculture that will last for 4 years from April 4, 2011. Infogest aims at building an open international network of institutes undertaking multidisciplinary basic research on food digestion gathering scientists from different origins (food scientists, gut physiologists, nutritionists...). The network gathers 70 partners from academia, corresponding to a total of 29 countries. The three main scientific goals are: Identify the beneficial food components released in the gut during digestion; Support the effect of beneficial food components on human health; Promote harmonization of currently used digestion models Infogest meetings highlighted the need for a publication that would provide researchers with an insight into the advantages and disadvantages associated with the use of respective in vitro and ex vivo assays to evaluate the effects of foods and food bioactives on health. Such assays are particularly important in situations where a large number of foods/bioactives need to be screened rapidly and in a cost effective manner in order to ultimately identify lead foods/bioactives that can be the subject of in vivo assays. The book is an asset to researchers wishing to study the health benefits of their foods and food bioactives of interest and highlights which in vitro/ex vivo assays are of greatest relevance to their goals, what sort of outputs/data can be generated and, as noted above, highlight the strengths and weaknesses of the various assays. It is also an important resource for undergraduate students in the ‘food and health’ arena.
Download or read book Damage Associated Molecular Patterns in Human Diseases written by Walter Gottlieb Land and published by Springer. This book was released on 2018-10-09 with total page 870 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents current understanding of the importance of modern immunology in the etiopathogenesis of human diseases and explores how this understanding is impacting on diagnosis, prognosis, treatment, and prophylaxis. As the core of modern immunology, the “danger/injury model” is introduced and addressed throughout the book. Volume I of the book describes the network of damage-associated molecular pattern molecules (DAMPs) and examines the central role of DAMPs in cellular stress responses and associated regulated cell death, the promotion and resolution of inflammation, the activation of innate lymphoid cells and unconventional T cells, the stimulation of adaptive immunity, and tissue repair. The significance of DAMPs in a wide range of human diseases will then be explored in Volume II of the book, with discussion of the implications of injury-induced innate immunity for present and future treatments. This book is written for professionals from all medical and paramedical disciplines who are interested in the introduction of innovative data from immunity and inflammation research into clinical practice. The readership will include practitioners and clinicians such as hematologists, rheumatologists, traumatologists, oncologists, intensive care anesthetists, endocrinologists such as diabetologists, psychiatrists, neurologists, pharmacists, and transplantologists.
