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Current Opinion in Immunology

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https://www.readbyqxmd.com/read/27907816/nucleic-acid-sensing-tlrs-trafficking-and-regulation
#1
REVIEW
Olivia Majer, Bo Liu, Gregory M Barton
Toll-like receptors (TLRs) play an important role in innate immune responses against pathogenic microorganisms or tissue damage. Nucleic acid (NA)-sensing TLRs localize in intracellular vesicular compartments and recognize foreign-derived and host-derived nucleic acid ligands. Inappropriate activation of NA-sensing TLRs can cause pathogenic inflammation and autoimmunity. Multiple regulatory mechanisms exist to limit recognition of self-NAs. This review summarizes recent progress that has been made in understanding how NA-sensing TLRs are regulated via trafficking, proteolytic cleavage, as well as ligand processing and recognition...
November 28, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27855321/plasmacytoid-dendritic-cells-in-autoimmunity
#2
REVIEW
Santosh K Panda, Roland Kolbeck, Miguel A Sanjuan
Plasmacytoid dendritic cells (pDC) is a unique cell population that produces large amounts of type I interferon upon recognition of nucleic acids placing them at the crossroad of both innate and adaptive immunity. Their ability to produce interferon makes them central to anti-viral responses. They are also responsive to circulating autoantibodies bound to nuclear antigens and in that scenario the release of interferons initiate self-directed immune responses. There are now a growing number of autoimmune disorders where unabated activation of pDC is suspected to be pathogenic...
November 14, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27842238/alternative-inflammasome-activation-enables-il-1%C3%AE-release-from-living-cells
#3
REVIEW
Moritz M Gaidt, Veit Hornung
Classical modes of NLRP3 activation entail a priming step that enables its activation (signal 1) and a potassium efflux-dependent activation signal (signal 2) that triggers pyroptosome formation and pyroptosis, a lytic cell death necessary for IL-1β release. Opposing to that, human monocytes engage an alternative NLRP3 inflammasome pathway in response to LPS that proceeds in the absence of signal 2 activation and enables IL-1β secretion without pyroptosis. This specifically relies on Caspase-8 to propagate signaling to NLRP3, leading to inflammasome activation in absence of pyroptosome formation...
November 11, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27842237/early-innate-immune-responses-to-bacterial-lps
#4
REVIEW
Charles V Rosadini, Jonathan C Kagan
A mammalian receptor for bacterial lipopolysaccharide (LPS), Toll-like receptor 4 (TLR4), plays a beneficial role in controlling bacterial infections, but is also a main driver of aberrant inflammation in lethal sepsis. As a result, investigation of TLR4 signaling has been a major area of research. Despite this focus, our understanding of the mechanisms that regulate TLR4 activities remains primitive. Nowhere is our knowledge of TLR4 biology more lacking than at the receptor-proximal level, where many factors act in concert to regulate LPS signaling...
November 11, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27839940/editorial-overview-autoimmunity
#5
EDITORIAL
Kathryn Haskins, Jane Hoyt Buckner
No abstract text is available yet for this article.
November 10, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27835762/il-15-signaling-in-nk-cell-cancer-immunotherapy
#6
REVIEW
Jai Rautela, Nicholas D Huntington
While cancer has been traditionally treated by chemotherapy, radiation, targeted therapies and surgery, a fifth pillar of cancer treatment, immunotherapy, has emerged over the past 10 years and revolutionized our war on cancer. The benchmark for drugs in this category has been set by the development of CD8 T cell checkpoint (CTLA-4 and PD-1/PD-L1) inhibitors. These therapies effectively expand and reactivate the pool of tumor-specific T cells leading to objective response rates of up to 50% in patients with certain cancers...
November 8, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27821272/targeting-cytokine-signaling-in-autoimmunity-back-to-the-future-and-beyond
#7
REVIEW
Kiyoshi Hirahara, Daniella Schwartz, Massimo Gadina, Yuka Kanno, John J O'Shea
Cytokines represent structurally diverse soluble factors with critical roles in normal immune function and the pathogenesis of autoimmunity. The emergence of many successful biological therapies targeting cytokines and cytokine receptors exemplifies the importance of cytokines in driving human autoimmune disease; unsurprisingly, there is no paucity of reviews on this subject. Nonetheless, many patients with autoimmune disease do not respond to biologicals, and cure remains an unmet goal. Thus, targeting the intracellular pathways employed by cytokines provides new therapeutic opportunities...
November 4, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27764715/understanding-mechanisms-of-autoimmunity-through-translational-research-in-vitiligo
#8
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
https://www.readbyqxmd.com/read/27745972/advances-in-food-allergy-oral-immunotherapy-toward-tolerance
#9
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
https://www.readbyqxmd.com/read/27723537/a-roadmap-of-the-generation-of-neoantigens-as-targets-of-the-immune-system-in-type-1-diabetes
#10
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
https://www.readbyqxmd.com/read/27623177/editorial-overview-allergy-and-hypersensitivity
#11
James McCluskey, Robyn E O'Hehir
No abstract text is available yet for this article.
September 9, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27744240/t-cell-exhaustion-and-immune-mediated-disease-the-potential-for-therapeutic-exhaustion
#12
REVIEW
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...
December 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27718448/endoplasmic-reticulum-stress-in-beta-cells-and-autoimmune-diabetes
#13
REVIEW
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...
December 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27718447/targeting-b-cells-in-treatment-of-autoimmunity
#14
REVIEW
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...
December 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27710840/macrophages-and-dendritic-cells-in-islets-of-langerhans-in-diabetic-autoimmunity-a-lesson-on-cell-interactions-in-a-mini-organ
#15
REVIEW
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...
December 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27710839/environmental-control-of-autoimmune-inflammation-in-the-central-nervous-system
#16
REVIEW
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...
December 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27636649/t-cells-in-systemic-lupus-erythematosus
#17
REVIEW
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...
December 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27504587/dna-reactive-b-cells-in-lupus
#18
REVIEW
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...
December 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27619413/the-concept-of-allergen-associated-molecular-patterns-aamp
#19
REVIEW
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...
October 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27326654/toll-like-receptor-2-in-host-defense-against-mycobacterium-tuberculosis-to-be-or-not-to-be-that-is-the-question
#20
REVIEW
Archana Gopalakrishnan, Padmini Salgame
Toll-like receptor (TLR) 2 is expressed on immune cells and respiratory epithelial cells lining the lung. TLR2 is not critical for protection during acute Mycobacterium tuberculosis (Mtb) infection but it has a significant multi-faceted role in containing chronic infection. This review highlights the contribution of TLR2 to host protection, immune evasion by Mtb and immune regulation during chronic Mtb infection. The TLR2-triggered pro-inflammatory cytokines initiate protective mechanisms and limit Mtb replication while the immune evasion pathways counterattack anti-bacterial effector mechanisms...
October 2016: Current Opinion in Immunology
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