Auswirkungen der Hautbarrierestörung in Filaggrin- und Hornerin(FlgHrnr)-defizienten Mäusen auf den atopischen Marsch

Loss-of-function mutations in skin barrier proteins, such as filaggrin (Flg) and hornerin (Hrnr), are known major risks for atopic dermatitis (AD) and the further development of asthma, a process known as atopic march. The present study investigated whether AD-like dermatitis in barrier-impaired filaggrin- and hornerin-deficient (FlgHrnr -/-) mice, compared with wild-type mice, promotes allergen sensitization and enhances clinical signs for asthma. Therefore, mice were repeatedly treated topically with MC903, resulting in the development of an AD-like phenotype, a skin reaction clinically and immunologically similar to human AD. In parallel, all animals were subjected to intraperitoneal injections of ovalbumin (OVA) and subsequent provocation of the airways with OVA containing aerosol, resulting in allergic airway inflammation. It could be shown that immunological processes induced by MC903 can lead to facilitated sensitization but also exacerbation of experimental asthma in FlgHrnr -/- mice. This was shown by increased production of Th2-type immunoglobulins such as IgE and OVA-specific IgG1 and a higher proportion of inflammatory infiltrates in the lung. These data suggest that loss-of-function mutations in the filaggrin/hornerin gene represent an important risk factor in the link of AD and the progression to the atopic march.2022-03-2