Surface expression of FcϵRI on Langerhans' cells of clinically uninvolved skin is associated with disease activity in atopic dermatitis, allergic asthma, and rhinitis

Background: FcϵRI expressed on the surface of human epidermal Langerhans' cells facilitates uptake of IgE-associated allergens and plays a pivotal role in the pathogenesis of atopic dermatitis. Seminal results from studies investigating Langerhans' cell FcϵRI in skin biopsy sections or epidermal cell suspensions demonstrate the highest receptor expression in lesional skin of patients with active atopic dermatitis. Objective: We sought to investigate and localize FcϵRI expression on Langerhans' cells within a minimally disturbed tissue environment in clinically uninvolved skin and to compare receptor expression between healthy donors and patients with atopic dermatitis or other allergic diseases. Methods: Intact epidermal sheets from skin suction blisters, immunofluorescently stained with Langerhans' cell markers and anti-FcϵRIα (mAbs 15E5 and 22E7) or anti-IgE, were examined by means of confocal microscopy. Samples incubated with anti-FcϵRIα before or after cell fixation-permeabilization were compared to discriminate between cytoplasmic and membrane localization. Results: Cytoplasmic FcϵRI α chain was found in Langerhans' cells from all donors, irrespective of atopic status. Surface FcϵRI-bound IgE was detected in the skin of individuals with active atopic dermatitis and in the skin of those with active asthma or rhinitis. No surface FcϵRI was expressed in the skin of patients with a clinical history of atopic dermatitis, asthma, or rhinitis whose disease was in remission or in the skin of nonatopic individuals. Conclusion: In clinically uninvolved skin, Langerhans' cell-surface FcϵRI expression is not only linked to atopic dermatitis but is also generally associated with allergic disease. This supports the concept of a systemic regulatory mechanism associated with active allergic disease, which is further aggravated by local inflammation in atopic skin lesions. (J Allergy Clin Immunol 2003;112:411-9.)