18Primary cilia are a unique organelle, known to provide a signaling hub for variety of cell 19 activities. Their potential role(s) in human immune homeostasis and diseases, however, have 20 yet to be explored. Here, we show that human dendritic cells (DCs) express primary cilia-like 21 structure. The primary cilia growth during DC proliferation by GM-CSF was shut off by DC 22 maturation agents, suggesting the role of primary cilia to transduce proliferation signaling. 23PDGFRα pathway, one of proliferation signal in primary cilia, promoted DC proliferation in a 24 dependent manner of intra-flagellar transport system. In epidermis with atopic dermatitis 25 patients, aberrant ciliated langerhans cells and keratinocytes with showing immature state 26 were observed that may play a potential role in inflammation and skin barrier disorder. 27
Primary cilia influence cell activity, and thus have a unique role in maintaining cell proliferation and differentiation. In atopic dermatitis (AD) and psoriasis, areas of skin inflammation exhibit dysregulated keratinocyte homeostasis. The role of primary cilia in these conditions remains unclear. The objectives of this study is to elucidate the incidence of primary cilia in skin inflammation and the potential mechanism underlying the dysregulation of keratinocytes. Primary cilia were observed using immunofluorescence staining. Normal skin samples were compared with skin samples from patients with AD or psoriasis in terms of cilia numbers and length. The effect of cytokine stimulation on ciliogenesis in keratinocytes was analysed using a primary keratinocyte culture. IFT88, an important ciliary intraflagellar protein, was blocked in Th2 and Th17 cytokines‐stimulated keratinocytes. These effects were analysed with quantitative polymerase chain reaction and Western blot. Significant increases in ciliated cells were observed in AD and psoriasis skin samples compared with normal skin samples. The stimulation of keratinocytes using Th2 and Th17 cytokines modulated the formation of primary cilia. The amount of IFT88 in the primary cilia associated with the phosphorylation of JNK, but not p38, in keratinocytes stimulated with interleukin‐13, 17A and 22. An increase of ciliated cells in the epidermis may impair keratinocyte differentiation under stress conditions caused by inflammation in both AD and psoriasis patients.
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