Claudin-1 decrease impacts epidermal barrier function in atopic dermatitis lesions dose-dependently

TY - JOUR

T1 - Claudin-1 decrease impacts epidermal barrier function in atopic dermatitis lesions dose-dependently

AU - Bergmann, Sophia

AU - von Buenau, Barbara

AU - Vidal-Y-Sy, Sabine

AU - Haftek, Marek

AU - Wladykowski, Ewa

AU - Houdek, Pia

AU - Lezius, Susanne

AU - Duplan, Hélène

AU - Bäsler, Katja

AU - Dähnhardt-Pfeiffer, Stephan

AU - Gorzelanny, Christian

AU - Schneider, Stefan W

AU - Rodriguez, Elke

AU - Stölzl, Dora

AU - Weidinger, Stephan

AU - Brandner, Johanna M

PY - 2020/2/6

Y1 - 2020/2/6

N2 - The transmembrane protein claudin-1 is a major component of epidermal tight junctions (TJs), which create a dynamic paracellular barrier in the epidermis. Claudin-1 downregulation has been linked to atopic dermatitis (AD) pathogenesis but variable levels of claudin-1 have also been observed in healthy skin. To elucidate the impact of different levels of claudin-1 in healthy and diseased skin we determined claudin-1 levels in AD patients and controls and correlated them to TJ and skin barrier function. We observed a strikingly broad range of claudin-1 levels with stable TJ and overall skin barrier function in healthy and non-lesional skin. However, a significant decrease in TJ barrier function was detected in lesional AD skin where claudin-1 levels were further reduced. Investigations on reconstructed human epidermis expressing different levels of claudin-1 revealed that claudin-1 levels correlated with inside-out and outside-in barrier function, with a higher coherence for smaller molecular tracers. Claudin-1 decrease induced keratinocyte-autonomous IL-1β expression and fostered inflammatory epidermal responses to non-pathogenic Staphylococci. In conclusion, claudin-1 decrease beyond a threshold level results in TJ and epidermal barrier function impairment and induces inflammation in human epidermis. Increasing claudin-1 levels might improve barrier function and decrease inflammation and therefore be a target for AD treatment.

AB - The transmembrane protein claudin-1 is a major component of epidermal tight junctions (TJs), which create a dynamic paracellular barrier in the epidermis. Claudin-1 downregulation has been linked to atopic dermatitis (AD) pathogenesis but variable levels of claudin-1 have also been observed in healthy skin. To elucidate the impact of different levels of claudin-1 in healthy and diseased skin we determined claudin-1 levels in AD patients and controls and correlated them to TJ and skin barrier function. We observed a strikingly broad range of claudin-1 levels with stable TJ and overall skin barrier function in healthy and non-lesional skin. However, a significant decrease in TJ barrier function was detected in lesional AD skin where claudin-1 levels were further reduced. Investigations on reconstructed human epidermis expressing different levels of claudin-1 revealed that claudin-1 levels correlated with inside-out and outside-in barrier function, with a higher coherence for smaller molecular tracers. Claudin-1 decrease induced keratinocyte-autonomous IL-1β expression and fostered inflammatory epidermal responses to non-pathogenic Staphylococci. In conclusion, claudin-1 decrease beyond a threshold level results in TJ and epidermal barrier function impairment and induces inflammation in human epidermis. Increasing claudin-1 levels might improve barrier function and decrease inflammation and therefore be a target for AD treatment.

U2 - 10.1038/s41598-020-58718-9

DO - 10.1038/s41598-020-58718-9

M3 - SCORING: Journal article

C2 - 32029783

VL - 10

SP - 2024

JO - SCI REP-UK

JF - SCI REP-UK

SN - 2045-2322

IS - 1

ER -