한빛사논문
- 조회628
Min-Jung Park1,5, Youngjae Park 2,5, Jeong Won Choi1, Jin-Ah Baek1,3, Ha Yeon Jeong1,3, Hyun Sik Na1,3, Young-Mee Moon1, Mi-La Cho 1,3,4,6 and Sung-Hwan Park1,2,6
1The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
2Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
3Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea.
4Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea.
5These authors contributed equally: Min-Jung Park,Youngjae Park.
6These authors contributed equally: Mi-La Cho, Sung-Hwan Park.
Corresponding authors : Correspondence to Mi-La Cho or Sung-Hwan Park.
Abstract
Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by inflammation, microangiopathy, and progressive fibrosis in the skin and internal organs. To evaluate the pathophysiologic mechanisms and efficacies of potential therapeutics for SSc, a preclinical model recapitulating the disease phenotypes is needed. Here, we introduce a novel animal model for SSc using immunodeficient mice injected with peripheral blood mononuclear cells (PBMCs) from SSc patients. Human PBMCs acquired from SSc patients and healthy controls were transferred into NOD.Cg-PrkdcscidIl2rgtm1Wjl (NSG) mice with concurrent bleomycin injection. Blood, skin, and lung tissues were acquired and analyzed after PBMC engraftment. In addition, we investigated whether the humanized murine model could be used to assess the efficacy of potential therapeutics for SSc. Human PBMCs from SSc patients and healthy controls were engrafted into the blood, skin, and lung tissues of NSG mice. Histological analysis of affected tissues from mice treated with SSc PBMCs (SSc hu-mice) demonstrated substantial inflammation, fibrosis and vasculopathy with human immune cell infiltration and increased expression of IL-17, TGF-β, CCL2, CCL3, and CXCL9. The proportions of circulating and tissue-infiltrating T helper 17 (Th17) cells were elevated in SSc hu-mice. These cells showed increased expression of CXCR3 and phosphorylated STAT3. SSc hu-mice treated with rebamipide and other potential Th17-cell-modulating drugs presented significantly reduced tissue fibrosis. Mice injected with patient-derived PBMCs show promise as an animal model of SSc.
논문정보
- Research article
- 2022년 09월 (BRIC 등록일 2022-11-18)
- 국내 연구진
- 생명과학 > 면역학
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