Expression of Toll-like receptors in nasal epithelium in allergic rhinitis.

Toll-like receptors (TLRs) are important in barrier homeostasis, but their role in airborne allergies is not fully understood. The aim was to evaluate baseline and allergen-induced expression of TLR proteins in nasal epithelium during allergic rhinitis. Nineteen otherwise healthy non-smoking volunteers both allergic to birch pollen and non-allergic controls were enrolled. We took nasal biopsies before and after off-seasonal intranasal birch pollen or diluent challenge. The expression of epithelial TLR1-7, TLR9-10, and MyD88 proteins was immunohistochemically evaluated from the nasal biopsies. The TLR1-3 and TLR5-10 mRNAs were observed by RNA-microarray. Baseline epithelial expression of TLR proteins was wide and identical in controls and atopics. After off-seasonal intranasal birch pollen challenge, a negative change in the expression score of TLR1 and TLR6 proteins was detected in the atopic group. TLR mRNA expression was not affected by birch pollen challenge. Nasal epithelium seems to express all known TLRs. The mechanisms by which TLR1, and TLR6 proteins could affect pollen allergen transport need further studies.

Allergen interactions with epithelium.

PURPOSE OF REVIEW: Allergies are a global health problem with rapidly increasing prevalence but still lacking pathogenetic knowledge or optimal treatment. The objective is to add to the conventional thinking that allergies are caused by overactive, mainly T-cell-mediated, immunological responses and thus to raise the putative role of altered epithelial functions. RECENT FINDINGS: Birch pollen allergen was rapidly and actively transported through the respiratory epithelium via caveolar-dependent mechanisms only in patients allergic to birch pollen but not their healthy controls. Transcriptomic analyses showed that whereas healthy individuals raised a strong epithelial response after intranasal allergen challenge, the allergic patients had a reduced response. Thus allergies could also be due to hyporeactive responses on the epithelial level. SUMMARY: Epithelium has emerged as an active and complex organ with mechanical, biochemical and immunological functions. The increasing awareness that epithelium interacts actively with allergens might provide new targets for the prevention and management of allergy.

Allergens are transported through the respiratory epithelium.

We used a top-down approach with a wide repertoire of wet laboratory and in silico techniques for analyzing the pathogenesis of early events within the type I allergic reactions. We could show a caveolar-dependent transport of the birch pollen allergen through the respiratory epithelium of allergic patients but not of their healthy controls. The application of discovery-driven methodologies can provide new hypotheses worth further analyses of complex multifactorial diseases such as type I allergy.

Direct in vivo monitoring of acute allergic reactions in human conjunctiva.

Immediate allergic reactions are initiated by allergen-induced, specific IgE-mediated mast cell degranulation and involve leukocyte recruitment into the inflamed site. We compared conjunctival signs, symptoms, and in vivo leukocyte rolling and extravasation into sites of inflammation in five patients allergic to birch pollen and in 10 nonallergic controls who received a challenge to birch allergen or histamine. Both the specific allergen in allergic patients and histamine, both in patients and in healthy controls, induced symptoms and signs of an immediate allergic reaction together with leukocyte rolling within the conjunctival blood vessels. However, only allergen, not histamine, caused leukocyte extravasation into the site of inflammation in the allergic patients. Allergen also increased expression of endothelial P-selectin in conjunctival vessels and slowed the rolling of leukocytes which is required for their extravasation from blood circulation into the target tissue. Finally, i.v. heparin strongly reduced the number of slowly rolling cells during allergen- or histamine-induced reactions and this can probably hinder the leukocyte extravasation after allergen exposure. These findings suggest that slow rolling is required for leukocyte extravasation in acute allergic reactions, and it can be inhibited by heparin in vivo in therapeutically relevant conditions.