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Current Opinion in Immunology

James P Strassner, John E Harris
Vitiligo is an autoimmune disease of the skin that leads to life-altering depigmentation and remains difficult to treat. However, clinical observations and translational studies over 30-40 years have led to the development of an insightful working model of disease pathogenesis: Genetic risk spanning both immune and melanocyte functions is pushed over a threshold by known and suspected environmental factors to initiate autoimmune T cell-mediated killing of melanocytes. While under cellular stress, melanocytes appear to signal innate immunity to activate T cells...
October 17, 2016: Current Opinion in Immunology
Deborah M Hussey Freeland, Hua Fan-Minogue, Jonathan M Spergel, Talal A Chatila, Kari C Nadeau
The incidence of food allergy, a disease characterized by adverse immune responses that can render common foods life-threatening, is rising. Yet our current standard of care is simply avoidance of allergenic foods and administration of emergency medications upon accidental exposure. Significant advances have been made in food allergy oral immunotherapy, which is emerging as a potential preventive and curative treatment for this disease. The fundamental strategy of oral immunotherapy is to mitigate adverse immune responses to allergenic food proteins through repeated exposure; reduced reactivity to food allergens (desensitization) often results, but the establishment of sustained immune unresponsiveness or of permanent resolution (tolerance) is not certain...
October 13, 2016: Current Opinion in Immunology
Eoin F McKinney, Kenneth Gc Smith
T cell exhaustion represents a continuous spectrum of cellular dysfunction induced during chronic viral infection, facilitating viral persistence and associating with poor clinical outcome. Modulation of T cell exhaustion can restore function in exhausted CD8 T cells, promoting viral clearance. Exhaustion has also been implicated as playing an important role in anti-tumour responses, whereby exhausted tumour-infiltrating lymphocytes fail to control tumour progression. More recently exhaustion has been linked to long-term clinical outcome in multiple autoimmune diseases but, in contrast to cancer or infection, it is associated with a favourable clinical outcome characterised by fewer relapses...
October 13, 2016: Current Opinion in Immunology
Bart O Roep, Maria Jl Kracht, Menno van Lummel, Arnaud Zaldumbide
Type 1 diabetes (T1D) is an autoimmune disease characterized by the selective destruction of the insulin-producing beta cells. Beta cell dysfunction caused by an inflammatory microenvironment is believed to trigger the peripheral activation of CD4 and CD8 autoreactive T cells. This review will compile post-transcriptional and post-translational modifications (PTM) involved in the generation of beta cell neoantigens and proposes a reconstruction of the sequence of events connecting environmental changes and autoimmunity...
October 7, 2016: Current Opinion in Immunology
Amy L Clark, Fumihiko Urano
Type 1 diabetes results from the autoimmune destruction of pancreatic β cells, leading to insulin deficiency and hyperglycemia. Although multiple attempts have been made to slow the autoimmune process using immunosuppressive or immunomodulatory agents, there are still no effective treatments that can delay or reverse the progression of type 1 diabetes in humans. Recent studies support endoplasmic reticulum (ER) as a novel target for preventing the initiation of the autoimmune reaction, propagation of inflammation, and β cell death in type 1 diabetes...
October 5, 2016: Current Opinion in Immunology
S Elizabeth Franks, Andrew Getahun, P Mark Hogarth, John C Cambier
B cells have emerged as effective targets for therapeutic intervention in autoimmunities in which the ultimate effectors are antibodies, as well as those in which T cells are primary drivers of inflammation. Proof of this principle has come primarily from studies of the efficacy of Rituximab, an anti-CD20 mAb that depletes B cells, in various autoimmune settings. These successes have inspired efforts to develop more effective anti-CD20s tailored for specific needs, as well as biologicals and small molecules that suppress B cell function without the risks inherent in B cell depletion...
October 5, 2016: Current Opinion in Immunology
Javier A Carrero, Stephen T Ferris, Emil R Unanue
Islets of Langerhans of all species harbor a small number of resident macrophages. These macrophages are found since birth, do not exchange with blood monocytes, and are maintained by a low level of replication. Under steady state conditions, the islet macrophages are in an activated state. Islet macrophages have an important homeostatic role in islet physiology. At the start of the autoimmune process in the NOD mouse, a small number of CD103+ dendritic cells (DC) are found at about the same time that CD4+ T cells also appear in islets...
October 3, 2016: Current Opinion in Immunology
Veit Rothhammer, Francisco J Quintana
Multiple sclerosis (MS) is a chronic autoimmune inflammatory demyelinating disorder of the central nervous system (CNS), which causes severe disability and requires extensive medical attention and treatment. While the infiltration of pathogenic immune cells into the CNS leads to the formation of inflammatory lesions in its initial relapsing-remitting stage, late stages of MS are characterized by progressive neuronal loss and demyelination even without continued interaction with the peripheral immune compartment...
October 3, 2016: Current Opinion in Immunology
Abel Suárez-Fueyo, Sean J Bradley, George C Tsokos
Systemic Lupus Erythematosus is an autoimmune disorder caused by a complex combination of genetic, epigenetic and environmental factors. Different polymorphisms and epigenetic modifications lead to altered gene expression and function of several molecules which lead to abnormal T cell responses. Metabolic and functional alterations result in peripheral tolerance failures and biased differentiation of T cells into pro-inflammatory and B cell-helper phenotypes as well as the accumulation of disease-promoting memory T cells...
September 13, 2016: Current Opinion in Immunology
James McCluskey, Robyn E O'Hehir
No abstract text is available yet for this article.
September 9, 2016: Current Opinion in Immunology
Isabella Pali-Schöll, Erika Jensen-Jarolim
For proteins to become allergenic, they need to acquire features enabling them to induce B cell activation and isotype switch to IgE production. Crosslinking of the B-cell receptor (BCR) is the most efficient way to productively activate B-cells. The IgE-crosslinking capability of allergens is equally crucial in the effector phase of immediate type allergy. Antigens, which acquire enhanced crosslinking capacity by oligomerization, aggregation, or the expression of repetitive epitopes may therefore gain allergenic potency...
September 9, 2016: Current Opinion in Immunology
Hideki Ueno
Studies with mouse models have established the pathogenic roles of T follicular helper (Tfh) cells in antibody-mediated autoimmune diseases. In contrast, evidence in human autoimmune pathogenesis has been lacking for years. Recent progress in understanding on the biology of human Tfh cells and on the approaches assessing their response has enabled gaining insights into the alterations of Tfh response and the underlying mechanisms. For example, increase of circulating Tfh (cTfh) cells expressing PD-1 and/or ICOS and alterations in the composition of cTfh subsets have emerged as a common feature in a broad range of autoimmune diseases...
August 30, 2016: Current Opinion in Immunology
Paul Zhou, Zheng W Chen
No abstract text is available yet for this article.
August 20, 2016: Current Opinion in Immunology
Anne M Pesenacker, Laura Cook, Megan K Levings
FOXP3 controls the development and function of T regulatory cells (Tregs). Autoimmunity is linked to changes in FOXP3 activity that can occur at multiple levels and lead to Treg dysfunction. For example, changes in IL-2 signaling, FOXP3 transcription and/or post-translational modifications can all contribute to loss of self-tolerance. As additional pathways of FOXP3 regulation are elucidated, new therapeutic approaches to increase Treg activity either by cell therapy or pharmacological intervention are being tested...
August 18, 2016: Current Opinion in Immunology
Øyvind Bruserud, Bergithe E Oftedal, Anette B Wolff, Eystein S Husebye
The gene causing the severe organ-specific autoimmune disease autoimmune polyendocrine syndrome type-1 (APS-1) was identified in 1997 and named autoimmune regulator (AIRE). AIRE plays a key role in shaping central immunological tolerance by facilitating negative selection of T cells in the thymus, building the thymic microarchitecture, and inducing a specific subset of regulatory T cells. So far, about 100 mutations have been identified. Recent advances suggest that certain mutations located in the SAND and PHD1 domains exert a dominant negative effect on wild type AIRE resulting in milder seemingly common forms of autoimmune diseases, including pernicious anemia, vitiligo and autoimmune thyroid disease...
August 6, 2016: Current Opinion in Immunology
Jolien Suurmond, Justine Calise, Susan Malkiel, Betty Diamond
IgG anti-DNA antibodies are both diagnostic and pathogenic for systemic lupus erythematosus (SLE). They contribute to tissue inflammation through direct tissue binding and to systemic inflammation through activation of Toll-like receptors by nucleic acid-containing immune complexes. IgG DNA-reactive antibodies originate when B cell tolerance mechanisms are impaired. The heterogeneous immune perturbations in SLE lead to the survival and activation of DNA-reactive B cells in various B cell subsets at distinct stages of B cell maturation and differentiation...
August 6, 2016: Current Opinion in Immunology
Zheng W Chen
Recent observation that prenyl pyrophosphates bind the Ig superfamily protein butyrophilin 3A1 (BTN3A1) suggests that modifying BTN3A1 activates major γδ T-cell subset, Vγ2Vδ2 T cells. Studies also show that microbial phosphoantigen HMBPP is required for expansion, pulmonary response, effector functions and memory polarization of Vγ2Vδ2 T cells during infections. Broad repertoires of cytokines involve expansion, recall-like expansion and effector functions of Vγ2Vδ2 T cells after Mtb infection or vaccination...
August 1, 2016: Current Opinion in Immunology
Ton N Schumacher, Nir Hacohen
Somatic mutations in the genome represent one of the major drivers of malignancy. However, non-synonymous mutations are also a source of mutated peptides that are presented by HLA molecules to induce protective CD4 and CD8 T cell responses. Consistent with this notion, the mutation burden of a tumor is correlated with local immunity as well as outcome of therapy and patient survival. Furthermore, neoantigen-specific T cells appear sufficient to control tumors prophylactically and therapeutically. While the role of neoantigens as a determinant of the foreignness of human cancers is now well established, major questions, including the relative importance of clonal vs subclonal neoantigens, and CD4 vs CD8 T cells, remain unanswered...
August 2016: Current Opinion in Immunology
Ton N Schumacher, Nir Hacohen
No abstract text is available yet for this article.
August 2016: Current Opinion in Immunology
Rino Rappuoli, Ennio De Gregorio
No abstract text is available yet for this article.
August 2016: Current Opinion in Immunology
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