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

Erika Jensen-Jarolim,Franziska Roth-Walter,Isabella Pali-Schöll

doi:10.1097/aci.0000000000000364

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.

Highlights

Failure in innate defense mechanisms often is the first step toward atopic and allergic diseases
Mouse models of allergen immunotherapy are challenging for the following reasons: allergy mouse models rely on allergen application in context with Th2 adjuvants and thereby induce robust disease that is difficult to modulate; symptomatic allergy in mice is, unlike in humans, associated with immunoglobulin E (IgE) and IgG1; mice express Tregs, but do not harbor immunoglobulin G4 (IgG4) antibodies which is an important biomarker in human allergen immunotherapy [1]
In a murine atopic dermatitis model, epicutanous application of ovalbumin in conjunction with CpG was effective for treatment by promoting a strong Th1-mediated immune response leading to a decrease in antigen-specific IgE and increase in IgG2a antibodies [45]

Summary

INTRODUCTION

Failure in innate defense mechanisms (inborn or acquired barrier leakage of skin and mucosa and misbalanced microbiome) often is the first step toward atopic and allergic diseases. Animal models should help us mimicking these pathophysiological conditions and should allow proof-of-concept studies for the efficacy of novel therapies with a certain predictive value for humans. Many aspects of mouse models are suitable to picture the human condition in its extreme and were very successfully used in current animal models of allergy and immunomodulation. Several immune parameters can be directly compared between animal models and humans; for instance, mice harbor natural killer T cells, dendritic cells ( lacking FceRI in wild type mice) and regulatory T-cells (Tregs). Mouse models are limited, e.g. because of the absence of the immunoglobulin G4 (IgG4). Animal models on immunomodulation in atopy and allergy Jensen-Jarolim et al

KEY POINTS

CONCLUSION