Induction of immunologic tolerance of food allergens by use of regulatory dendritic cells
The outcomes of food allergies can range from hives to fatal anaphylaxis. While allergen avoidance fully prevents these reactions, vanishingly low-level exposure to some allergens can trigger lethal responses. Specific immunotherapy (SIT) has proven useful for some allergies, but SIT is cumbersome, dangerous if not used correctly, and is not uniformly effective. Oral immunotherapies (OIT) for food allergies have attracted a great deal of attention lately and they can dramatically increase the dose of allergen required to induce allergic reactions, but OIT also comes with very significant caveats. We have developed a novel, regulatory dendritic cell (DCreg) therapy that can reverse asthma and food allergies in animal models, and have now shown that human DCreg can reverse allergen sensitivity among T cells of allergic individuals. We propose to develop human DCreg for use in food allergic individuals, as assessed in vitro and, funds permitting, in vivo in humanized mouse models.
CAAIF Food Allergy Research Grant
DR. JOHN GORDON
Investigating treatment of Children with Chronic Hives
Urticaria (acute and chronic) is the fourth most prevalent allergic condition after rhinitis, asthma and drug allergy,but the number of patients who visit emergency departments due to urticaria is higher compared to these otherallergic diseases. Children with chronic urticaria (CU) have a substantial impairment of Health-related quality of life(patients suffering from CU scored in the lowest 25th percentile on physical impact) and significantly lower schoolperformance compared with the impact of other allergic diseases. Although no studies assessing the prevalence ofCU in Canadians had been published so far, assuming a similar 3% lifetime prevalence found in other countries, it islikely that over 1,000,000 Canadians will be affected by CU at some point in their life. The primary treatment for CUis high doses (up to 4 times normal dose) of antihistamines. However in many patients this does not bring relief.These cases are often prescribed omalizumab as an alternative treatment. We are interested in determining factorsimplicated in these cases where high dose antihistamines are not effective as well as the effectiveness of thealternative treatment.
Aralez Canada Pharmaceutical Inc. and CAAIF Research Grant in Allergic Rhinitis or Urticaria
DR. MOSHE BEN-SHOSHAN
Understanding the role of the human gut virome in the development of early-onset asthma
The microbial composition of the human gut has received a great deal of attention in the past decade due to its implications in health and diseases. While the vast majority of research focuses on bacteria, phages are also found in the gut where they outnumber bacteria by a factor of ten. Phages are known to massively kill bacterial populations and interact with our immune system. Recently, our collaborators at EarlyVir (Denmark) have found robust evidence that a skewed bacterial composition in the gut during the first year of life affects the risk of early-onset asthma. But what about gut phages? Given their abundance in this ecosystem, do phages play a role in the development of asthma? The impact of phages on our health remains poorly understood in general as their characterization is challenging and requires tailored and multidisciplinary approaches.
Asthma Canada/CAAIF Graduate Student Awards
Nociceptor neurons control pollution-exacerbating asthma
Half of the severe asthma patients suffer from uncontrolled exacerbations. Although several classes of drugs control asthma symptoms and help abort attacks, there is no available treatment that accelerates the resolution of inflammation. Recent advances suggest that airway pollution, including fine particular matter (FPM), exacerbates severe allergic airway inflammation (AAI). Our work in neuro-immunology has shown that, in the context of asthma, vagal nociceptor neurons drive a feed-forward inflammatory loop with lung immune cells, and that silencing these neurons reverses AAI. Recent data highlight neuronal expression of aryl hydrocarbon receptor (AhR) sensing of air pollution to the induction of atopic dermatitis. Overall, by acting upstream of lung type 2-inflammatory immune cells, targeting vagal AhR-nociceptors may constitute a promising therapeutic avenue to resolve pollution-exacerbating AAI.