Outstanding animal studies in allergy II. From atopic barrier and microbiome to allergen-specific immunotherapy

Abstract

Purpose of reviewAnimal studies published within the past 18 months were assessed, focusing on innate and specific immunomodulation, providing knowledge of high translational relevance for human atopic and allergic diseases.Recent findingsAllergic companion animals represent alternative models, but most studies were done in mice. Atopic dermatitis mouse models were refined by the utilization of cytokines like IL-23 and relevant skin allergens or enzymes. A novel IL-6 reporter mouse allows biomonitoring of inflammation. Both skin pH and the (transferable) microflora have a pivotal role in modulating the skin barrier. The microflora of the gastrointestinal mucosa maintains tolerance to dietary compounds and can be disturbed by antiacid drugs. A key mouse study evidenced that dust from Amish households, but not from Hutterites protected mice against asthma. In studies on subcutaneous and sublingual allergen-specific immunotherapy, much focus was given on delivery and adjuvants, using poly-lacto-co-glycolic particles, CpGs, probiotics or Vitamin D3. The epicutaneous and intralymphatic routes showed promising results in mice and horses in terms of prophylactic and therapeutic allergy treatment.SummaryIn atopic dermatitis, food allergies and asthma, environmental factors, together with the resident microflora and barrier status, decide on sensitization versus tolerance. Also allergen-specific immunotherapy operates with immunomodulatory principles.

Microcrystalline Tyrosine and Aluminum as Adjuvants in Allergen-Specific Immunotherapy Protect from IgE-Mediated Reactivity in Mouse Models and Act Independently of Inflammasome and TLR Signaling

“…Our study demonstrates that MCT has adjuvant properties, making it a good alternative to alum-based AIT. Of course, murine studies have limited value with regard to the clinical potential of a novel adjuvant in human AIT because they use rather unnatural sensitization methods and because mice are short of biological factors that are considered important in human AIT (e.g., IgG4) ( 50 , 51 ). However, murine studies can contribute to the understanding of the mechanism by which a novel adjuvant acts.…”

Comparing immediate‐type food allergy in humans and companion animals—revealing unmet needs

“…Factors influencing oral tolerance are the integrity of the intestinal epithelial barrier, tolerance‐inducing antigen‐presenting cells (APC), and T‐regulatory cells . The known risk factors for atopic dermatitis are the same in humans and in companion animals and are also associated with a higher risk for food allergy …”

“…25 The known risk factors for atopic dermatitis are the same in humans and in companion animals and are also associated with a higher risk for food allergy. 37,38…”

Contributions of innate lymphocytes to allergic responses

“…Since it is difficult to investigate these pathways in humans, animal models that can be experimentally manipulated have provided an invaluable resource and have greatly informed our understanding of allergic inflammation. Some of the most commonly used animal systems employ sensitization strategies with model antigens such as ovalbumin (OVA), treatment with proteases that damage the epithelium such as papain, administration of cytokines including recombinant interleukin (IL) −33, as well as exposure to common allergens such as those found in house dust mite (HDM), Alternaria alternata, and Aspergillus fumigatus extracts (Table 1) (7)(8)(9). Collectively, these models have provided insight into the cellular and molecular mechanisms promoting allergy-associated pathology and have revealed major roles for type 2 and type 17 cytokines in driving allergic inflammation.…”