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The Role of Epidermal Primary Cilia in Atopic Dermatitis and Psoriasis

Rizaldy, Defri 大阪大学 DOI:10.18910/82187

2021.03.24

概要

Primary cilia, a tiny organelle structure, is recognized by its important role in cellular maintenance including cell proliferation and differentiation by regulating multiple signaling pathways. Recently, it has become clear that the severity of diseases such as polycystic kidney disease and various cancers have been correlated with primary cilia. With regard to skin inflammation, especially atopic dermatitis and psoriasis, keratinocyte development has been severely deregulated. The purpose of this study is to understand the role of primary cilia in keratinocytes in inflammation condition. It will help to deepen the knowledge regarding the pathophysiology of inflammatory skin disorder and lead to the novel therapy.

By this awareness, I confirmed the increase in epidermal primary cilia distribution in atopic dermatitis and psoriasis skin compared to normal skin sample. Thereafter, observation in primary keratinocyte showed that stimulation using Th2 and Th17 cytokines increased primary cilia formation, but stimulation using Th1 cytokines did not increase ciliogenesis. Moreover, I introduced the downregulation of desmoglein-1, a keratinocyte differentiation protein in primary keratinocyte, after knockdown of (Intraflagellar Transport Protein 88) IFT88, an essential protein in primary cilia.

Additionally, IFT88 showed be to associated with phosphorylation of JNK, a stress-related signaling pathway in primary keratinocyte. These results suggested that primary cilia have important role on modulating keratinocyte differentiation. These finding provide a novel perspective for characterizing the phenomena of skin inflammation that irregular ciliogenesis found in atopic dermatitis and psoriasis correspond with a decline in keratinocyte maturation and the generation of defects in the skin structure.

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