초록 ▼

- 본 연구에서는 아토피 피부염 mouse 모델과 아토피 피부염 환아들의 혈청을 이용하여 아토피 피부염의 면역학적 병인 기전을 분석해 보고 TH17 세포 관련 싸이토카인 등의 면역학적 변화에 의한 아토피 피부염에서의 피부 장벽 기능의 역할 및 기능을 규명해 보고자 하였음
- Oxazolone을 이용하여 아토피 피부염을 유발시켰을 때 wild type에 비하여 IL-17 null mutant mice에서 귀의 부종 정도, 염증 세포 동원 및 TH2 유형의 싸이토카인들이 현저하게 감소하는 것을 확인할 수 있었음
- 경표피 수

- 본 연구에서는 아토피 피부염 mouse 모델과 아토피 피부염 환아들의 혈청을 이용하여 아토피 피부염의 면역학적 병인 기전을 분석해 보고 TH17 세포 관련 싸이토카인 등의 면역학적 변화에 의한 아토피 피부염에서의 피부 장벽 기능의 역할 및 기능을 규명해 보고자 하였음
- Oxazolone을 이용하여 아토피 피부염을 유발시켰을 때 wild type에 비하여 IL-17 null mutant mice에서 귀의 부종 정도, 염증 세포 동원 및 TH2 유형의 싸이토카인들이 현저하게 감소하는 것을 확인할 수 있었음
- 경표피 수분손실량, 각질층의 지질 분포 및 층판소체(lamellar body) 형태 변화 등을 측정하여 피부장벽의 기능 손상을 확인하였을 때, wild type에서는 현저한 피부장벽의 기능 손상을 확인할 수 있었으나, IL-17 null mutant mice에서는 장벽 손상이 감소하는 것을 역시 확인할 수 있었음
- 또한 아토피 피부염을 가진 환자의 혈청 IL-17 값이 대조군에 비해 유의하게 증가되어 있음을 확인하였고, 혈청 IL-17 값은 피부장벽손상이 심한 중증군에서 경증군에 비해 유의하게 증가됨을 확인할 수 있었음
- 이러한 연구 결과들로 미루어 아토피 피부염에서의 면역이상이나 피부장벽손상의 조절에 IL-17이 중요한 역할을 담당하고 있다는 것을 확인할 수 있었음

Abstract ▼

I. Background: Atopic dermatitis is a chronic and relapsing inflammatory skin disease. The pathophysiology of AD is complex. Atopic dermatitis (AD) is characterized by dermal inflammatory infiltrates with a dominant Th2 profile during the acute phase, whereas a Th1 profile is characteristic of the c

I. Background: Atopic dermatitis is a chronic and relapsing inflammatory skin disease. The pathophysiology of AD is complex. Atopic dermatitis (AD) is characterized by dermal inflammatory infiltrates with a dominant Th2 profile during the acute phase, whereas a Th1 profile is characteristic of the chronic stage. Interleukin (IL)-17 is a proinflammatory cytokine produced by Th17 cells. There are six family members of IL-17, designated by the letters A-F. Levels of the IL-17 members IL-17A, IL-17E and IL-17F, and of IL-17-producing cells, are known to increase in skin patients with psoriasis or AD.
II. Aim: In this study, we investigated whether IL-17 regulates immune dysregulation and affects skin barrier in oxazolone (OXA)-induced AD-like and CD-like disease models in mice, by comparing IL-17 null mutant (IL-17-/-) versus wild-type (WT) mouse strains in the models. And we also examined the association of serum IL-17F levels and disease severity in children with atopic dermatitis.
III. Methods: IL-17-/- and WT Balb/c mice were used for OXA induction of AD-like and CD-like skin diseases. Ear swelling was measured by a micrometer. Skin biopsies were obtained for RNA isolation and histology. Real-time quantitative PCR analysis was performed to quantify mRNA expression of Th2 cytokines. Skin permeability was measured by a vapometer, and structural changes in the skin were evaluated by electron and confocal microscopy. For the study of AD children, ELISA was used to measure IL-17F in the sera of 228 patients with atopic dermatitis and 62 healthy children.
IV. Results: Both OXA-induced AD and CD responses were alleviated in IL-17-/- mice relative to WT, demonstrated by reductions in ear swelling, inflammatory cell infiltration and levels of Th2 cytokines. These endpoints were used to characterize inflammatory dysregulation in both AD and CD models. Skin barrier dysfunction, measured by increases in transepidermal water loss and dysfunction of lamellar bodies, and reductions in lipid distribution, were seen in both AD and CD in WT mice. In IL-17-/- mice, however, these responses were significantly diminished. In accord with these findings, the mean serum level of IL-17F in study group was significantly higher than that of control group. IL-17F was also higher in the patients with severe AD than in those with mild AD.
V. Conclusions: The results indicate that the IL-17 may play a role in modulating immune dysregulation and affecting skin barrier in OXA-induced AD-like and CD-like skin disease models in the Balb/c mouse and human AD patients.