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IL-21 drives skin and lung inflammation and fibrosis in a model for systemic sclerosis.
Um, In Gyu; Woo, Jin Seok; Lee, Young Joon; Lee, Seon-Yeong; Jeong, Ha Yeon; Na, Hun Sik; Lee, Jeong Su; Lee, A Ram; Park, Sung-Hwan; Cho, Mi-La.
Afiliación
  • Um IG; Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea; Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; Department of Biomedic
  • Woo JS; Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea; Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
  • Lee YJ; Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea; Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; Department of Biomedic
  • Lee SY; Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea; Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
  • Jeong HY; Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea; Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
  • Na HS; Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea; Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
  • Lee JS; Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea; Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; Department of Biomedic
  • Lee AR; Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea; Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
  • Park SH; Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
  • Cho ML; Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea; Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; Department of Biomedic
Immunol Lett ; 270: 106924, 2024 Sep 12.
Article en En | MEDLINE | ID: mdl-39260526
ABSTRACT

BACKGROUND:

Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, abnormal inflammation, and fibrosis of the skin and internal organs, notably the skin and lungs, significantly impairing quality of life. There is currently no cure for SSc, and its etiology remains largely unknown, presenting a primary barrier to effective treatment. We investigated the role of interleukin-21 (IL-21) in the pathogenesis of SSc.

METHODS:

We assessed the expression levels of fibrosis-related genes in human dermal fibroblasts exposed to IL-21 and TGF beta. We also induced SSc in wild-type C57BL/6 mice and IL-21 knockout (KO) mice with a C57BL/6 background using bleomycin (Bleomycin). Histological analyses were conducted on skin and lung tissues from these mice. The distribution and expression levels of fibrosis-related proteins in the tissues were examined via immunohistochemistry and quantitative real-time PCR. Furthermore, we measured the frequency of Th1, Th2, and Th17 cells among splenocytes through flow cytometry.

RESULTS:

IL-21 activation led to STAT3 phosphorylation more than TGF beta in dermal fibroblasts. In IL-21 KO mice with BLM-induced SSc, skin thickness and lung fibrosis were reduced. The absence of IL-21 in these mice resulted in suppressed expression of fibrosis-related genes, including Col1a1, Col1a2, Col3a1, CTGF, α-SMA, STAT3, and TGFß, in the skin and lungs. It also led to a decreased frequency of Th1, Th2, and Th17 cells, as well as a lower Th17/Treg ratio among splenocytes, factors known to contribute to the development of SSc.

CONCLUSIONS:

IL-21 contributes to the development of SSc by promoting the expression of fibrosis-related genes and modulating the levels of CD4+ T cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Immunol Lett Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Immunol Lett Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos