연구성과 홍보

Sci Rep. 2023 Sep 16;13(1):15405.

Title : Regulation of psoriasis, colitis, and the intestinal microbiota by clusterin

Authors : Yu Kyung Jun1,2, Hee Tae Yoon2, So Hyun Kwon2, Ui Hyeon Jo3, Ji Eun Kim4, Yoo Min Han2,5, Min-Seon Kim6, Jong Pil Im2, Dong Ho Lee1, Joo Sung Kim2, Seong-Joon Koh7*, Hyunsun Park8,9,10*

Affiliations :

1Division of Gastroenterology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

2Laboratory of Intestinal Mucosa and Skin Immunology, Liver Research Institute and Seoul National University College of Medicine, Seoul, Korea.

3Department of Dermatology, SMG-SNU Boramae Medical Center, Seoul, Korea.

4Department of Pathology, SMG-SNU Boramae Medical Center, Seoul, Korea.

5Department of Internal Medicine and Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea.

6Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea.

7Laboratory of Intestinal Mucosa and Skin Immunology, Liver Research Institute and Seoul National University College of Medicine, Seoul, Korea. jel1206@snu.ac.kr.

8Laboratory of Intestinal Mucosa and Skin Immunology, Liver Research Institute and Seoul National University College of Medicine, Seoul, Korea. snuhdm@gmail.com.

9Department of Dermatology, SMG-SNU Boramae Medical Center, Seoul, Korea. snuhdm@gmail.com.

10Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea. snuhdm@gmail.com.

DOI: 10.1038/s41598-023-42019-y

Abstract :

Psoriasis, a chronic and systemic inflammatory disorder characterized by activation of the interleukin (IL)-23/IL-17 axis, may be associated with the intestinal microbiota through the so-called "gut-skin axis." Clusterin is a glycoprotein ubiquitously distributed in mammalian tissues; however, its role in psoriasis is unclear. Therefore, we evaluated the role of clusterin in psoriatic skin inflammation, systemic inflammation, and colitis using a murine model of IMQ-induced psoriasis. In IMQ-treated clusterin-knockout (clusterin-/-) mice, the expressions of inflammatory cytokines in clusterin-silenced human keratinocytes and intestinal microbial composition were analyzed. We also examined clusterin expression in the skin tissues of patients with psoriasis. IMQ-induced psoriatic skin inflammation is suppressed in clusterin-/- mice. Long-term administration of IMQ induced systemic inflammation and colitis; however, both were alleviated by the genetic deletion of clusterin. Genetic silencing of clusterin in human keratinocytes inhibited the production of inflammatory cytokines involved in the initiation and progression of psoriasis. The composition of the intestinal microbiota in IMQ-treated clusterin-/- and wild-type mice was different. Genetic deletion of clusterin suppressed the increase in the Firmicutes/Bacteroidetes (F/B) ratio. Skin tissues of patients with psoriasis showed high clusterin expression. In conclusion, inhibition of clusterin decreased psoriatic skin inflammation, systemic inflammation, colitis, and altered the F/B ratio in an IMQ-induced murine psoriasis model.