Keratinocyte proline-rich protein modulates immune and epidermal response in imiquimod-induced psoriatic skin inflammation.

Abstract

Psoriasis is a persistent inflammatory skin disease thought to arise as a result of the infiltration of inflammatory cells and activation of keratinocytes. Recent advances in basic research and clinical experience revealed that the interleukin (IL)-23/IL-17 axis has been identified as a major immune pathway in psoriasis. However, it remains unclear how keratinocyte factors contribute to the pathology of psoriasis. Keratinocyte proline-rich protein (KPRP) is a proline-rich insoluble protein, which is present in the epidermis and is likely to be involved in the skin barrier function. Here, to investigate the potential roles of KPRP in psoriatic skin inflammation, Kprp-modified mice were applied in the imiquimod (IMQ)-induced skin inflammation model, which develops psoriasis-like epidermal hyperplasia and cutaneous inflammation features. Then, heterozygous knockout (Kprp+/- ) but not homozygous knockout (Kprp-/- ) mice displayed attenuated skin erythema compared to control wild-type mice. In addition, RNA sequencing, quantitative PCR and/or histological analysis detected changes in the expression of several molecules related to psoriatic inflammation or keratinocyte differentiation in Kprp+/- mice, but not Kprp-/- mice. Further analysis exhibited reduced IL-17-producing γδlow T cells and amplified epidermal hyperplasia in Kprp+/- mice, which were implied to be related to decreased expression of β-defensins and increased expression of LPAR1 (Lysophosphatidic acid receptor 1), respectively. Thus, our results imply that KPRP has the potential as a therapeutic target in psoriatic skin inflammation.