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Seminars in Immunopathology

Marco Donia, Magnus Pedersen, Inge Marie Svane
Patients with preexisting active autoimmune disorders were excluded from clinical trials of immune checkpoint inhibitors. However, patients with autoimmune disorders are diagnosed with cancer at least as frequently as the global population, and clinicians treating patients outside clinical trials have generally been reluctant to offer cancer immunotherapy to this patient group. In this brief article, we review the most recent literature on the efficacy and safety of CTLA-4- and PD-1-blocking antibodies in patients with preexisting autoimmune disorders...
October 11, 2016: Seminars in Immunopathology
Thorbjørn Krejsgaard, Lise M Lindahl, Nigel P Mongan, Mariusz A Wasik, Ivan V Litvinov, Lars Iversen, Erik Langhoff, Anders Woetmann, Niels Odum
Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome...
October 7, 2016: Seminars in Immunopathology
Mads Hald Andersen
Our initial understanding of immune-regulatory cells was based on the discovery of suppressor cells that assure peripheral T-cell tolerance and promote immune homeostasis. Research has particularly focused on the importance of regulatory T cells (Tregs) for immune modulation, e.g. directing host responses to tumours or inhibiting autoimmunity development. However, recent studies report the discovery of self-reactive pro-inflammatory T cells-termed anti-regulatory T cells (anti-Tregs)-that target immune-suppressive cells...
September 27, 2016: Seminars in Immunopathology
Maisa C Takenaka, Francisco J Quintana
Deficits in immunological tolerance against self-antigens and antigens provided by the diet and commensal microbiota can result in the development of inflammatory and autoimmune disorders. Dendritic cells (DCs) are pivotal regulators of the immune response, specialized in antigen presentation to drive T cell priming and differentiation. DCs also have a tolerogenic function, participating in the enforcement of central and peripheral tolerance and the resolution of ongoing immune responses. Thus, DCs control effector and regulatory mechanisms relevant to the pathology of autoimmune disorders...
September 19, 2016: Seminars in Immunopathology
Morten Hansen, Mads Hald Andersen
Though present in low numbers, dendritic cells (DCs) are recognized as major players in the control of cancer by adaptive immunity. The roles of cytotoxic CD8(+) T-cells and Th1 helper CD4(+) T-cells are well-documented in murine models of cancer and associated with a profound prognostic impact when infiltrating human tumors, but less information is known about how these T-cells gain access to the tumor or how they are primed to become tumor-specific. Here, we highlight recent findings that demonstrate a vital role of CD103(+) DCs, which have been shown to be experts in cross-priming and the induction of anti-tumor immunity...
September 16, 2016: Seminars in Immunopathology
Claudia Cristina Motran, Laura Fernanda Ambrosio, Ximena Volpini, Daiana Pamela Celias, Laura Cervi
The effective defense against parasite infections requires the ability to mount an appropriate and controlled specific immune response able to eradicate the invading pathogen while limiting the collateral damage to self-tissues. Dendritic cells are key elements for the development of immunity against parasites; they control the responses required to eliminate these pathogens while maintaining host homeostasis. Ligation of dendritic cell pattern recognition receptors by pathogen-associated molecular pattern present in the parasites initiates signaling pathways that lead to the production of surface and secreted proteins that are required, together with the antigen, to induce an appropriate and timely regulated immune response...
September 1, 2016: Seminars in Immunopathology
Ran Orgad, Bar Nathansohn-Levi, Sivan Kagan, Yair Reisner
The recently described generation of a highly defined population of dendritic cells which express perforin and granzyme A (termed "perf-DCs") and their ability to selectively delete cognate CD8+ T cell has raised the possibility that these cells play a role in the maintenance of peripheral tolerance. Using bone marrow transplantation, we generated mice selectively lacking perforin expressing dendritic cells. These mice progressively gain weight and exhibit features resembling metabolic syndrome as well as an enhanced susceptibility to autoimmunity induction...
August 30, 2016: Seminars in Immunopathology
Ari Waisman, Dominika Lukas, Björn E Clausen, Nir Yogev
Dendritic cells (DC) are unique hematopoietic cells, linking innate and adaptive immune responses. In particular, they are considered as the most potent antigen presenting cells, governing both T cell immunity and tolerance. In view of their exceptional ability to present antigen and to interact with T cells, DC play distinct roles in shaping T cell development, differentiation and function. The outcome of the DC-T cell interaction is determined by the state of DC maturation, the type of DC subset, the cytokine microenvironment and the tissue location...
July 25, 2016: Seminars in Immunopathology
Petra Clara Arck
No abstract text is available yet for this article.
November 2016: Seminars in Immunopathology
Marcus Altfeld, Madeleine J Bunders
No abstract text is available yet for this article.
November 2016: Seminars in Immunopathology
Stefan M Gold, Rhonda R Voskuhl
Translational research generally refers to a "bench to bedside" approach where basic science discoveries in models move to clinical trials in humans. However, a "bedside to bench to bedside" approach may be more promising with respect to clinical relevance, since it starts with a clinical observation that can serve as a research paradigm to elucidate mechanisms and translate them back into novel therapeutic approaches. The effect of pregnancy on human autoimmune disorders in general, and multiple sclerosis (MS) in particular, serves as an intriguing example of how this can be used to understand disease pathobiology and discover new therapeutic targets...
November 2016: Seminars in Immunopathology
María Emilia Solano, Megan C Holmes, Paul R Mittelstadt, Karen E Chapman, Eva Tolosa
Endogenous levels of glucocorticoids rise during pregnancy to warrant development and maturation of the fetal organs close to birth. However, during most of the gestation, the fetus is protected from excessive biologically active endogenous glucocorticoids by placental and fetal expression of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2). Maternal stress, which may overwhelm placental 11β-HSD2 activity with high glucocorticoid levels, or administration of synthetic glucocorticoids to improve the survival chances of the premature newborn, are associated to postnatal increased risk for immune diseases...
November 2016: Seminars in Immunopathology
Yoshinori Yamanishi, Hajime Karasuyama
No abstract text is available yet for this article.
September 2016: Seminars in Immunopathology
Kaori Mukai, Mindy Tsai, Philipp Starkl, Thomas Marichal, Stephen J Galli
IgE-dependent mast cell activation is a major effector mechanism underlying the pathology associated with allergic disorders. The most dramatic of these IgE-associated disorders is the fatal anaphylaxis which can occur in some people who have developed IgE antibodies to otherwise innocuous antigens, such as those contained in certain foods and medicines. Why would such a highly "maladaptive" immune response develop in evolution and be retained to the present day? Host defense against parasites has long been considered the only beneficial function that might be conferred by IgE and mast cells...
September 2016: Seminars in Immunopathology
Landon K Oetjen, Mario Noti, Brian S Kim
Basophils have become increasingly recognized as important innate immune cells that mediate antihelminth immunity and barrier inflammation. Recent discoveries have uncovered previously unrecognized heterogeneity in basophil populations. However, how diversity in basophil regulation and function impacts human disease remains poorly defined. The goal of the present review is to highlight how new insights into basophil heterogeneity can help us to better understand disease pathogenesis and inform the development of new therapeutics...
September 2016: Seminars in Immunopathology
Atsushi Otsuka, Yumi Nonomura, Kenji Kabashima
Mast cells and basophils are associated with T helper 2 (Th2) immune responses. Newly developed mast cell-deficient mice have provided evidence that mast cells initiate contact hypersensitivity via activating dendritic cells. Studies using basophil-deficient mice have also revealed that basophils are responsible for cutaneous Th2 skewing to haptens and peptide antigens but not to protein antigens. Recently, several studies reported the existence of innate lymphoid cells (ILCs), which differ from classic T cells in that they lack the T cell receptor...
September 2016: Seminars in Immunopathology
Yoshinori Yamanishi, Hajime Karasuyama
Recent studies demonstrated that basophils play crucial and non-redundant roles in the immune system, in spite of the fact that they are the rarest granulocytes and represent less than 1 % of peripheral blood leukocytes. In response to various stimuli, basophils release effector molecules stored in their cytoplasmic granules, including chemical mediators and proteases, and also secrete cytokines and chemokines. In this review, we will focus on the physiological and pathological roles of basophil-derived IL-4...
September 2016: Seminars in Immunopathology
Hideaki Morita, Hirohisa Saito, Kenji Matsumoto, Susumu Nakae
Mast cells are important immune cells for host defense through activation of innate immunity (via toll-like receptors or complement receptors) and acquired immunity (via FcεRI). Conversely, mast cells also act as effector cells that exacerbate development of allergic or autoimmune disorders. Yet, several lines of evidence show that mast cells act as regulatory cells to suppress certain inflammatory diseases. Here, we review the mechanisms by which mast cells suppress diseases.
September 2016: Seminars in Immunopathology
Shih Han Tsai, Kiyoshi Takeda
Adenosine 5'-triphosphate (ATP) is released from dying or damaged cells, as well as from activated cells. Once secreted, extracellular ATP induces several immune responses via P2X and P2Y receptors. Basophils and mast cells release ATP upon FcεRI-crosslinking, and ATP activates basophils and mast cells in an autocrine manner. Nucleotide-converting ectoenzymes, such as E-NTPD1, E-NTPD7, and E-NPP3, inhibit ATP-dependent immune responses by hydrolyzing ATP, thereby contributing to immune response regulation...
September 2016: Seminars in Immunopathology
Hua Huang, Yapeng Li, Bing Liu
Basophils and mast cells have long been known to play critical roles in allergic disease and in immunity against parasitic infection. Accumulated evidence also supports that basophils and mast cells have important roles in immune regulations, host defense against bacteria and viruses, and autoimmune diseases. However, origin and molecular regulation of basophil and mast cell differentiation remain incompletely understood. In this review, we focus on recent advances in the understanding of origin and molecular regulation of mouse and human basophil and mast cell development...
September 2016: Seminars in Immunopathology
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