Children's Hospital Colorado

Impact of Acute Local Allergen Exposure on Tissue Eosinophils Within Remote Organs

May 18, 2021

Points for parents:

  • Allergic diseases are currently the most common childhood conditions.
  • Allergic reactions in the gut, skin or respiratory tract typically cause inflammation in just that area.
  • In this study, Children’s Colorado researchers show, for the first time, how a local allergic reaction may also impact multiple organs.

Points for providers:

  • Our researchers sought to determine if tissue eosinophils within mucosal organs along the skin:lung:gut axis would be modulated by allergic inflammation in remote organs.
  • They modified mouse models of local skin, gut or lung allergen exposure to achieve acute models that elicited local eosinophilic inflammation similar to human atopic dermatitis, food allergy and asthma.
  • The study found that the frequency and phenotype of tissue eosinophils in remote mucosal organs was modulated and associated with priming for subsequent allergic disease.

Stats:

  • Approximately 20% of the worldwide population are affected by allergic diseases.
  • Approximately 64% of patients with eosinophilic esophagitis have a co-existing or previous allergic disease.

Research background: local allergen exposure and increase in tissue eosinophil

Historical data suggests there is a progressive and causal relationship between allergic disorders of the skin, lung and gut collectively referred to as the “allergic march,” suggesting mucosal organ crosstalk.

Mechanisms that link local allergic reactions to remote organs along the skin:lung:gut axis are unknown.

Researchers in the Digestive Health Institute at Children’s Hospital Colorado hypothesized that (1) the frequency of the tissue eosinophils in distant organs may increase in response to local allergic reactions and (2) this cellular response may prime mucosal organs for future allergic reactions.

Research methods: recreating acute models of allergic inflammation in mice

Researchers created three modified acute models of allergic inflammation localized to the skin, respiratory system and gastrointestinal tract to model the “allergic march” in mice. Allergen-sensitive mice were exposed to direct allergic challenges to the gut, respiratory system and skin. Researchers studied the frequency and phenotype of eosinophils within remote, allergen non-exposed organs along the skin:lung:gut axis.

The study used two groups of mice: one sensitized with the protein antigen ovalbumin (OVA) with an alum adjuvant admixture, and a control group sensitized with a PBS-alum admixture. After sensitization, both groups were challenged (the first group with OVA and the second group with PBS vehicle control) by direct administration to the skin, lung or gut for three consecutive days.

In some experiments, researchers determined whether mouse airways were primed for subsequent allergic disease by exposing both groups of mice to inhaled house dust mite, a common allergen trigger in people with asthma.

Research results: assessing tissues at the site of allergen exposure

For each of the three acute allergic disease models, tissue recovered four days after the final allergen challenge from the respective sites of allergen exposure (such as the skin, lung or gut) revealed local eosinophilic infiltration. For example, in the AD model, inflammation manifested as an increase in dermis eosinophils and OVA administration to the gut elicited an increase in jejunum eosinophils.

Topical or endotracheal allergen challenge

  • Further examination of a potential link between acute local inflammation in the skin and lung on tissue eosinophils within remote intestinal tissues was examined by sampling jejunum tissue four days after the final challenge.
  • The sample demonstrated a near doubling of the total number of eosinophils within remote intestinal tissues.
  • Researchers observed increased numbers of lamina propria (LP) eosinophils in areas surrounding crypts and along the length of the villi.

Direct allergen topical and oral exposure

  • Low levels of eosinophils were observed in the steady state in healthy lungs. In the studied tissue, increased frequencies of eosinophils were detected within the lung as early as one day after allergen challenge.
  • In contrast to the homeostatic phenotype of steady state lung eosinophils, a majority of eosinophils detected within the lung following oral allergen exposure exhibited an inflammatory phenotype.
  • Oral or topical allergen exposure were found to prime the airways for a more robust allergic response to inhaled house dust mites.

Research conclusion: relationship between local gut, skin or respiratory allergic reactions and eosinophils

The study indicated a bidirectional relationship between local acute gastrointestinal, skin or respiratory allergic reactions and an increase in the frequency of eosinophils within remote mucosal tissues. This provides new insights into the allergic disease progressions of the gut, skin and respiratory systems.

Since other studies demonstrated differences in these relationships, study authors recommend further research to help define the mechanisms that regulate eosinophil infiltration and accumulation within remote organs.

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