Evidence for lysosomal dysfunction within the epidermis in psoriasis and atopic dermatitis.

Klapan, Kim; Frangež, Živa; Markov, Nikita; Yousefi, Shida; Simon, Dagmar; Simon, Hans-Uwe (2021). Evidence for lysosomal dysfunction within the epidermis in psoriasis and atopic dermatitis. Journal of investigative dermatology, 141(12), 2838-2848.e4. Elsevier 10.1016/j.jid.2021.05.016

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Atopic dermatitis (AD) and psoriasis (PS) are frequent chronic inflammatory skin diseases. Autophagy plays a substantial role in the homeostasis of the organism. Loss or impairment of autophagy is associated with multiple diseases. To investigate the possibility that autophagy plays a role in AD and PS, we investigated the levels of key autophagy-related proteins (ATGs) in human skin specimens as well as in primary human epidermal keratinocytes exposed to inflammatory stimuli in vitro. While TNF-α facilitated the induction of autophagy in an initial phase, it reduced the levels and enzymatic activities of lysosomal cathepsins in later time periods resulting in autophagy inhibition. Therefore, tumor necrosis factor-α (TNF-α) appears to play a dual role in the regulation of autophagy. The relevance of these in vitro findings were supported by the observation that the protein levels of cathepsin D and L are decreased in both PS and AD skin specimens. Taken together, this study suggests that TNF-α blocks autophagy in keratinocytes following long-term exposure, a mechanism, which may contribute to the chronicity of inflammatory diseases of the skin and, perhaps, other organs.

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