IgE is the antibody isotype found at the lowest concentration in the circulation. However IgE can undeniably play an important role in mediating allergic reactions; best exemplified by the clinical ...benefits of anti-IgE monoclonal antibody (omalizumab) therapy for some allergic diseases. This review will describe our current understanding of the interactions between IgE and its main receptors FcεRI and CD23 (FcεRII). We will review the known and potential functions of IgE in health and disease: in particular, its detrimental roles in allergic diseases and chronic spontaneous urticaria, and its protective functions in host defense against parasites and venoms. Finally, we will present an overview of the drugs that are in clinical development or have therapeutic potential for IgE-mediated allergic diseases.
Allergic asthma is characterized by elevated levels of IgE antibodies, type 2 cytokines such as interleukin-4 (IL-4) and IL-13, airway hyperresponsiveness (AHR), mucus hypersecretion and ...eosinophilia. Approved therapeutic monoclonal antibodies targeting IgE or IL-4/IL-13 reduce asthma symptoms but require costly lifelong administrations. Here, we develop conjugate vaccines against mouse IL-4 and IL-13, and demonstrate their prophylactic and therapeutic efficacy in reducing IgE levels, AHR, eosinophilia and mucus production in mouse models of asthma analyzed up to 15 weeks after initial vaccination. More importantly, we also test similar vaccines specific for human IL-4/IL-13 in mice expressing human IL-4/IL-13 and the related receptor, IL-4Rα, to find efficient neutralization of both cytokines and reduced IgE levels for at least 11 weeks post-vaccination. Our results imply that dual IL-4/IL-13 vaccination may represent a cost-effective, long-term therapeutic strategy for the treatment of allergic asthma as demonstrated in mouse models, although additional studies are warranted to assess its safety and feasibility.
Gain-of-function mutations in NLRP3 are responsible for a spectrum of autoinflammatory diseases collectively referred to as "cryopyrin-associated periodic syndromes" (CAPS). Treatment of CAPS ...patients with IL-1-targeted therapies is effective, confirming a central pathogenic role for IL-1β. However, the specific myeloid cell population(s) exhibiting inflammasome activity and sustained IL-1β production in CAPS remains elusive. Previous reports suggested an important role for mast cells (MCs) in this process. Here, we report that, in mice, gain-of-function mutations in Nlrp3 restricted to neutrophils, and to a lesser extent macrophages/dendritic cells, but not MCs, are sufficient to trigger severe CAPS. Furthermore, in patients with clinically established CAPS, we show that skin-infiltrating neutrophils represent a substantial biological source of IL-1β. Together, our data indicate that neutrophils, rather than MCs, can represent the main cellular drivers of CAPS pathology.
Introduction. Basil (Ocimum basilicum L.) is a little-known crop in the Bolivian highlands as its response to water use efficiency (WUE) in a Walipini-type greenhouses. Objective. To evaluate the ...behavior of two varieties of basil and the water use efficiency (WUE) in the application of foliar biofertilizer in a Walipini-type greenhouse. Materials and methods. The experiment was installed at the Ventilla Ecological Farm, in the Central Highlands of Bolivia, with an experimental period of 135 days (July 13 to November 25), 2014. A factorial experiment with two factors (varieties: Nufar F1 and Italian Large Leaf) and two levels of foliar biofertilizer (Biol) was used under a completely randomized block design. Results. Through the WUE, specific leaf area, and net assimilation rate relationship, it was observed that basil had a better development in Walipini-type greenhouse (underground greenhouse) since biomass accumulation was not significantly affected. The results showed that the production of basil in this environment using foliar biofertilizer, Biol, differ mainly by the variety rather than by the doses of Biol, showing that Nufar F1 had better development. Conclusion. A significant relationship was observed between Nufar F1 and Italian large Leaf for biomass weight when applying Biol at two different levels. It shows that there does not necessarily have to be a positive and significant relationship between biomass accumulation and WUE, so it is presumed that basil can develops regularly in Walipini-type greenhouses under semi-arid region conditions.
Asthma is the most common chronic lung disease, affecting more than 250 million people worldwide. The heterogeneity of asthma phenotypes represents a challenge for adequate assessment and treatment ...of the disease. However, approximately 50% of asthma patients present with chronic type 2 inflammation initiated by alarmins, such as IL-33 and thymic stromal lymphopoietin (TSLP), and driven by the TH2 interleukins IL-4, IL-5 and IL-13. These cytokines have therefore become important therapeutic targets in asthma. Here, we discuss current knowledge on the structure and functions of these cytokines in asthma. We review preclinical and clinical data obtained with monoclonal antibodies (mAbs) targeting these cytokines or their receptors, as well as novel strategies under development, including bispecific mAbs, designed ankyrin repeat proteins (DARPins), small molecule inhibitors and vaccines targeting type 2 cytokines.
Gain-of-function mutations in NLRP3 are responsible for a spectrum of autoinflammatory diseases collectively referred to as “cryopyrin-associated periodic syndromes” (CAPS). Treatment of CAPS ...patients with IL-1–targeted therapies is effective, confirming a central pathogenic role for IL-1β. However, the specific myeloid cell population(s) exhibiting inflammasome activity and sustained IL-1β production in CAPS remains elusive. Previous reports suggested an important role for mast cells (MCs) in this process. Here, we report that, in mice, gain-of-function mutations in Nlrp3 restricted to neutrophils, and to a lesser extent macrophages/dendritic cells, but not MCs, are sufficient to trigger severe CAPS. Furthermore, in patients with clinically established CAPS, we show that skin-infiltrating neutrophils represent a substantial biological source of IL-1β. Together, our data indicate that neutrophils, rather than MCs, can represent the main cellular drivers of CAPS pathology.
No abstract available
L’asthme est une maladie pulmonaire chronique de très forte prévalence, touchant quatre millions de personnes en France et plus de 300 millions dans le monde 1. Bien que ...l’asthme soit une maladie hétérogène regroupant des phénotypes variés, environ la moitié des sujets asthmatiques développent une inflammation de type 2, caractérisée par des taux élevés d’anticorps de classe Ig(immunoglobuline)E, de cytokines de type Th2, comme l’interleukine 4 (IL-4) et IL-13, et par la présence de granulocytes éosinophiles dans les voies aériennes ...
PDF
