Ling Lei1, Zhi-Yi He2, Cheng Zhao1, Xue-Jiao Sun2, Xiao-Ning Zhong2. 1. Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. 2. Department of Respiratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Abstract
AIM: Systemic sclerosis (SSc) is characterized by immune abnormalities, progressive fibrosis of the skin and internal organs, and microvascular injury and damage. Interleukin-21 receptor (IL-21R) is expressed in the epidermis from patients with SSc. However, information describing the role of IL-21 in SSc is limited. METHODS: We established a mouse model of bleomycin (BLM)-induced fibrosis. The frequency of CD4(+) IL-21(+) T, CD4(+) IL-21R(+) T and IL-21(+) Th17 cells in peripheral blood, skin and lungs of BLM-induced mice were detected by flow cytometry; IL-21 levels in the peripheral blood were evaluated by enzyme-linked immunosorbent assay (ELISA). CD4(+) T cells were isolated from the spleen of BLM-induced and control mice and cultured in vitro alone or in the presence of mrIL-21 or mrIL-21 plus transforming growth factor (TGF)-β1. The frequency of Th17 cells was detected by flow cytometry; levels of IL-17 were evaluated by ELISA, and the expression of IL-17A and retinoic-acid-receptor-related orphan receptors gamma t (RORγt) messenger RNA were analyzed by real-time polymerase chain reaction. RESULTS: Compared to control mice, the frequency of CD4(+) IL-21(+) T, CD4(+) 21R(+) T and IL-21(+) Th17 cells and the levels of IL-21 were significantly increased in BLM-induced mice. The frequency of CD4(+) IL-21(+) T, CD4(+) 21R(+) T and IL-21(+) Th17 cells and the levels of IL-21 were correlated with dermal and pulmonary inflammation and fibrosis. In vitro analyses indicate that IL-21 promoted the differentiation of Th17 cells from CD4(+) cells isolated from the spleen of BLM-induced mice. CONCLUSION: IL-21 may play an important role in the pathogenesis of SSc as a Th17 effector cytokine, and IL-21 may induce the differentiation of Th17 cells in the BLM-induced SSc mouse model.
AIM: Systemic sclerosis (SSc) is characterized by immune abnormalities, progressive fibrosis of the skin and internal organs, and microvascular injury and damage. Interleukin-21 receptor (IL-21R) is expressed in the epidermis from patients with SSc. However, information describing the role of IL-21 in SSc is limited. METHODS: We established a mouse model of bleomycin (BLM)-induced fibrosis. The frequency of CD4(+) IL-21(+) T, CD4(+) IL-21R(+) T and IL-21(+) Th17 cells in peripheral blood, skin and lungs of BLM-induced mice were detected by flow cytometry; IL-21 levels in the peripheral blood were evaluated by enzyme-linked immunosorbent assay (ELISA). CD4(+) T cells were isolated from the spleen of BLM-induced and control mice and cultured in vitro alone or in the presence of mrIL-21 or mrIL-21 plus transforming growth factor (TGF)-β1. The frequency of Th17 cells was detected by flow cytometry; levels of IL-17 were evaluated by ELISA, and the expression of IL-17A and retinoic-acid-receptor-related orphan receptors gamma t (RORγt) messenger RNA were analyzed by real-time polymerase chain reaction. RESULTS: Compared to control mice, the frequency of CD4(+) IL-21(+) T, CD4(+) 21R(+) T and IL-21(+) Th17 cells and the levels of IL-21 were significantly increased in BLM-induced mice. The frequency of CD4(+) IL-21(+) T, CD4(+) 21R(+) T and IL-21(+) Th17 cells and the levels of IL-21 were correlated with dermal and pulmonary inflammation and fibrosis. In vitro analyses indicate that IL-21 promoted the differentiation of Th17 cells from CD4(+) cells isolated from the spleen of BLM-induced mice. CONCLUSION:IL-21 may play an important role in the pathogenesis of SSc as a Th17 effector cytokine, and IL-21 may induce the differentiation of Th17 cells in the BLM-induced SSc mouse model.