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Current Opinion in Immunology

Jesmond Dalli, Charles N Serhan
Understanding mechanisms that control immunity is central in the quest to gain insights into the etiopathology of many of the diseases that afflict modern societies. New results implicate the nervous system as a central player in controlling many aspects of both the innate and adaptive arms of the immune response. Furthermore it is now well appreciated that a novel group of autacoids termed as specialized proresolving mediators, which are enzymatically produced from essential fatty acids, orchestrate the immune response promoting the termination of inflammation as well as tissue repair and regeneration...
November 16, 2017: Current Opinion in Immunology
Eric Espinosa, Salvatore Valitutti
Mast cells are innate immune cells implicated in immune surveillance and defense. They are filled with secretory granules where a vast array of molecules endowed with multiple biological activities are stored. The process of granule secretion, named degranulation, is a tightly controlled biological phenomenon that allows mast cells to rapidly and efficiently release bioactive mediators in response to extracellular stimuli. MC degranulation allows fighting pathogens, limiting envenomation and contributes to tissue homeostasis...
November 13, 2017: Current Opinion in Immunology
David E Place, Thirumala-Devi Kanneganti
The inflammasome is a complex of proteins that through the activity of caspase-1 and the downstream substrates gasdermin D, IL-1β, and IL-18 execute an inflammatory form of cell death termed pyroptosis. Activation of this complex often involves the adaptor protein ASC and upstream sensors including NLRP1, NLRP3, NLRC4, AIM2, and pyrin, which are activated by different stimuli including infectious agents and changes in cell homeostasis. Here we discuss new regulatory mechanisms that have been identified for the canonical inflammasomes, the most recently identified NLRP9b inflammasome, and the new gasdermin family of proteins that mediate pyroptosis and other forms of regulated cell death...
November 9, 2017: Current Opinion in Immunology
Stefanie Kretschmer, Min Ae Lee-Kirsch
The monogenic type I interferonopathies comprise a heterogenous group of disorders of the innate immune system associated with constitutive activation of antiviral type I interferon (IFN). Despite a remarkable phenotypic diversity, type I interferonopathies are commonly characterized by autoinflammation and varying degrees of autoimmunity or immunodeficiency. The elucidation of the underlying genetic causes has revealed novel cell-intrinsic mechanisms that protect the organism against inappropriate immune recognition of self nucleic acids by cytosolic sensors such as cGAS or MDA5 through metabolizing or processing of intracellular DNA or RNA...
November 9, 2017: Current Opinion in Immunology
Payel Sil, Ginger Muse, Jennifer Martinez
While classically considered a survival mechanism employed during nutrient scarcity, the autophagy pathway operates in multiple scenarios wherein a return to homeostasis or degradative removal of an invader is required. Now recognized as a pathway with vast immunoregulatory power, autophagy can no longer serve as a 'one size fits all' term, as its machinery can be recruited to different pathogens, at different times, with different outcomes. Both canonical autophagy and the molecularly related, yet divergent pathways non-canonical autophagy are key players in proper host defense and allow us an opportunity to tailor infectious disease intervention and treatment to its specific pathway...
November 7, 2017: Current Opinion in Immunology
Noel R Rose
Infections often precede the onset of autoimmune disease and molecular (or epitope) mimicry is a plausible link. Cross-reacting epitopes are common between an infecting microorganism and the host because negative selection of self-reactive T-cells and B-cells is frequently incomplete. Complete eradication could lead to major voids in the immunologic repertoire. The association of an autoimmune disease with a microbial epitope may signify a causal relationship with the organism, an indirect connection through bystander effects, persistent infection or coincidence...
November 2, 2017: Current Opinion in Immunology
Patricia Costa-Reis, Kathleen E Sullivan
Monogenic lupus is rare, but its study has contributed immensely to a better understanding of the pathogenesis of systemic lupus erythematosus. The first forms identified were inherited complement deficiencies, which predisposed to lupus due to impaired tolerance, and aberrant clearance of apoptotic bodies and immune complexes. In recent years, several new monogenic disorders with a lupus-like phenotype have been described. These include forms that affect nucleic acid repair, degradation and sensing (TREX1, DNASE1L3), the type I interferon (IFN) pathway (SAMHD1, RNASEH2ABC, ADAR1, IFIH1, ISG15, ACP5, TMEM173) and B cell development checkpoints (PRKCD; RAG2)...
October 27, 2017: Current Opinion in Immunology
Rui Martins, Sylvia Knapp
Heme is a vital, iron-containing prosthetic molecule present in a variety of proteins, of which hemoglobin is the most abundant. While the reactivity afforded by its central iron ion is essential for many cellular processes, it renders heme a potentially damaging molecule upon its release from hemeproteins, as it can catalyze the generation of reactive oxygen species. Severe intravascular hemolysis results in the leakage of vast amounts of hemoglobin, and subsequently, heme into the plasma. As such, heme is increasingly recognized as a major driving force for hemolysis-associated pathology including an increased risk for bacterial infections, due to its pro-oxidant, cytotoxic and immunomodulatory effects...
October 26, 2017: Current Opinion in Immunology
Lucy H Jackson-Jones, Cécile Bénézech
Natural IgM are crucial for early protection against infection and play an important homeostatic function by clearing dead cells. The production of IgM is ensured by a population of B cells with innate-like properties: their response is rapidly activated by innate signals early during the onset of infection. The main reservoir of innate-like B cells (IBCs) are the serous cavities, but their maintenance and activation depends on their relocation to a variety of lymphoid tissues. Recent advances indicate that fat-associated lymphoid clusters (FALCs) and milky spots contribute to local IgM secretion and play a central role in the localisation and regulation of IBC function...
October 24, 2017: Current Opinion in Immunology
Frédéric Rieux-Laucat
The autoimmune lymphoproliferative syndrome (ALPS) is a non-malignant and non-infectious uncontrolled proliferation of lymphocytes accompanied by autoimmune cytopenia. This clinical entity was recognized in the mid 60s and its genetic etiology was described in 1995 by the discovery of the FAS gene mutations. This was the first description of a monogenic cause of autoimmunity but its non-Mendelian expression remained elusive until the description of somatic and germline mutations in ALPS patients. The related apoptosis defect accounts for the accumulation of autoreactive lymphocytes as well as for specific clinical and biological features that distinguish the ALPS-FAS from other monogenic causes of ALPS such as somatic mutations of RAS or the recently described CTLA-4 insufficiency...
October 23, 2017: Current Opinion in Immunology
Irina Proekt, Corey N Miller, Michail S Lionakis, Mark S Anderson
AIRE is a well-established master regulator of central tolerance. It plays an essential role in driving expression of tissue-specific antigens in the thymus and shaping the development of positively selected T-cells. Humans and mice with compromised or absent AIRE function have markedly variable phenotypes that include a range of autoimmune manifestations. Recent evidence suggests that this variability stems from cooperation of autoimmune susceptibilities involving both central and peripheral tolerance checkpoints...
October 21, 2017: Current Opinion in Immunology
Yohko Kitagawa, Shimon Sakaguchi
Treg cells expressing the transcription factor Foxp3 are essential for immunological tolerance and homeostasis. Recent genome-wide studies have revealed that Foxp3(+) natural Treg cells possess a number of unique transcriptional and epigenetic features, which appear to be acquired along the course of Treg cell development and maintained throughout their lifespan. These studies also provide novel insights into how genomic variations contribute to genetic susceptibility to human autoimmune diseases by affecting Treg cell development and function...
October 21, 2017: Current Opinion in Immunology
Sabine Ivison, Christine Des Rosiers, Sylvie Lesage, John D Rioux, Megan K Levings
Autoimmunity results from an intersection of genetic and environmental factors that cause patient-specific perturbations in immune homeostasis. Defining autoimmunity-associated genetic factors has led to mechanistic insight into underlying etiologies, and the development of many biologic therapies that target the immune system. However, biomarker-informed pairing of patients with optimal biologic therapy is lacking. Here, we discuss platforms commonly used to find biomarkers that predict response to biologic therapy in autoimmunity and highlight recent biomarker discoveries...
October 17, 2017: Current Opinion in Immunology
Ruth Seelige, Stephen Searles, Jack D Bui
A cancer mass consists of a complex composition of cancer cells, stromal cells, endothelial cells and also immune cells, which can represent more than half of the cellularity of a solid cancer. These immune cells become activated when they sense cancer antigens and stress ligands. Innate immune cells also detect various aspects of cellular stress that characterize a growing tumor mass. These key hallmarks of cellular stress are also detected by the cancer cell itself. In this review, we highlight studies that show that the cancer cell itself could be considered an 'innate cell' that senses and reacts to non-immunologic hallmarks of cancer, including displaced nucleic acids, proteotoxic stress, oxidative stress, and metabolic alterations...
October 12, 2017: Current Opinion in Immunology
Nida Naushad, Ana Luisa Perdigoto, Jinxiu Rui, Kevan C Herold
Studies with immunologics have shown that the natural history of Type 1 diabetes can be modified. These studies have targeted key mediators of the disease and recent analyses, together with studies in preclinical models have identified mechanisms that may be involved in the clinical effects. Several issues remain including specificity of the interventions, adverse effects of the treatments, and duration of their effects. Future studies are likely to include more specific approaches with agents such as cell therapies with selected immune regulatory subsets, antigen specific therapies, and combinations of agents with complementary mechanisms of activity...
October 6, 2017: Current Opinion in Immunology
Calliope A Dendrou, Lars Fugger
Multiple sclerosis (MS) afflicts about 2.5 million people globally and poses a major personal and socioeconomic burden. The recognition of MS as an inflammatory disease, characterized by infiltration of immune cells into the central nervous system, has spurred research into the autoimmune etiology of the condition and has provided the rationale for its treatment through immunomodulation. Experience with immunotherapies in MS to date has suggested a disparity between the observed immune cell infiltration and the progressive loss of neurons...
September 16, 2017: Current Opinion in Immunology
Chamith Y Fonseka, Deepak A Rao, Soumya Raychaudhuri
CD4+ T cells have been long known to play an important role in the pathogenesis of rheumatoid arthritis (RA), but the specific cell populations and states that drive the disease have been challenging to identify with low dimensional single cell data and bulk assays. The advent of high dimensional single cell technologies-like single cell RNA-seq or mass cytometry-has offered promise to defining key populations, but brings new methodological and statistical challenges. Recent single cell profiling studies have revealed a broad diversity of cell types among CD4+ T cells, identifying novel populations that are expanded or altered in RA...
September 6, 2017: Current Opinion in Immunology
Fernando E Sepulveda, Geneviève de Saint Basile
Hemophagocytic lymphohistiocytosis (HLH, also referred to a hemophagocytic syndrome) is a life-threatening condition in which uncontrolled activation of lymphocytes and macrophages, and thus the secretion of large amounts of inflammatory cytokines, leads to a severe hyperinflammatory state. Over the last few decades, researchers have characterized primary forms of HLH caused by genetic defects that impair lymphocytes' cytotoxic machinery. Other genetic causes of HLH not related to impaired cytotoxicity have also recently been identified...
August 31, 2017: Current Opinion in Immunology
Marc Pellegrini, Elizabeth Hartland
No abstract text is available yet for this article.
October 2017: Current Opinion in Immunology
Milena Sokolowska, Cezmi A Akdis
Several recent key findings in immunology of allergic diseases that have led to a need of reassessment of our current thinking are reviewed in this issue of the journal. Recently developed strong evidence on the role of hygiene hypothesis in protection from allergic disease and its immune mechanisms is reviewed by Ober et al. The authors pointed out immunologic mechanisms of lower prevalence of asthma and allergic sensitization observed among Amish children living on traditional farms with higher endotoxin levels as compared to Hutterite children living on industrialized farms...
October 2017: Current Opinion in Immunology
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