집먼지 진드기 추출물이 사람 각질 세포주인 HaCaT에서 TARC생성과 IL-22수용체 발현 변화에 미치는 영향

Abstract

House dust mite (HDM) is known for one of factors that causes atopic dermatitis (AD). HDM aggravated symptoms of AD patient via the production of tumor necrosis factor (TNF)-α and interferon (IFN)-γ from keratinocyte. It is known that thymus and activation regulated chemokine (TARC) is highly expressed in AD lesion to recruit CCR4 expressing T cells. Interleukin (IL)-22, a member of IL-10 family, is produced by CD4+ T cell, natural killer (NK) cell and NKT cell. Its receptor is a heterodimer of IL-22Rα and IL-10Rβ. It is expressed on skin, pancreas, kidney and epithelial cells. In the skin of chronic AD patients, IL-22 is increased and shows pro-inflammatory effects. However, the effect of HDM on IL-22 production from T cells and on TARC production and IL-22Rα receptor expression in keratinocyte are largely unknown. Therefore, I investigated IL-22Rα expression and TARC production in human keratinocyte cell line, HaCaT by the treatment of HDM extract and their role in HDM-induced skin inflammation. As a result, HDM extract increased IL-22Rα expression and TARC production in HaCaT, although HDM extract could not remarkably increase of the proliferation of HaCaT. HDM extract enhanced TNF-α and IFN-γ production from T cells and it caused the increase TARC production from T cells. In addition, HDM extract increased IL-22 from T cells. Interestingly, I found that the production of IL-1α, IL-6 and TARC from HaCaT, when they were treated with rIL-22 or culture supernatant of HDM extract-treated T cells. It suggests that HDM extract induces the increase of IL-22 production from T cells, and then it produces IL-1α, IL-6 and TARC from HaCaT. Finally, I examined whether T cell migration is facilitated by culture supernatant of HDM extract-treated HaCaT, because I have already confirmed that TARC production is increased from HaCaT by HDM extract treatment. As I expected, T cell migration is increased by culture supernatant of HDM extract-treated HaCaT. Taken together, HDM extract not only increases IL-22Rα expression and TARC production in HaCaT, but also increases IL-22 production from T cells. And then, TARC production from HaCaT via the interaction between IL-22 and IL-22Rα facilitates T cell migration. And it might be one of the reason for inflammation in the skin lesion of AD patients.