Abstract
Aim To explore the role of group 2 innate lymphoid cells (ILC2s) in the pathogenesis of renal fibrosis in diabetic kidney disease (DKD). Methods The proportion of ILC2s and the levels of Th2 cytokines (IL-4, IL-5, and IL-13) in the peripheral blood of normal control subjects (NC) or patients with type 2 diabetes mellitus (DM), early diabetic kidney disease (DKD1), or late diabetic kidney disease (DKD2) were analyzed by flow cytometry and ELISA. The expression of transforming growth factor-β1 (TGF-β1), fibronectin (FN), collagen1, IL-4Rα, and IL-13Rα1 in renal tubular epithelial cells (HK-2) induced by IL-4, IL-13, or high glucose was analyzed by ELISA or qPCR. Results The proportion of ILC2s and the levels of IL-4, IL-5, and IL-13 were significantly increased in DKD patients and were positively correlated with the severity of DKD (P < 0.05). The expression of TGF-β1, FN, and collagen1 was significantly upregulated in HK-2 cells induced by IL-4 or IL-13 (P < 0.05). Moreover, the IL-4Rα and IL-13Rα1 mRNA in HK2 cells were increased followed by high glucose alone or combined with IL-4 or IL-13, but the differences were not statistically significant (P > 0.05). However, compared with high-glucose stimulation alone, the expression of TGF-β1, FN, and collagen1 was significantly increased in HK-2 cells induced by high glucose combined with IL-4 or IL-13 (P < 0.05). Conclusions ILC2s may participate in renal fibrosis in DKD partly via TGF-β1 signal pathway.
Highlights
Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease in the world [1, 2]
There were no significant differences in gender composition or age among the four groups (NC, diabetes mellitus (DM), DKD1, and DKD2), but there were significant differences in body mass index (BMI), systolic blood pressure (SBP), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), or white blood cell (WBC) number (P < 0 05)
Emerging evidences have shown that ILC2s mediate multiple types of tissue fibrosis such as intestinal fibrosis, hepatic fibrosis, and pulmonary fibrosis by secreting Th2 cytokines and regulating type 2 immunity [10, 15]
Summary
Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease in the world [1, 2]. Recent studies indicated that immune system activation and imbalance of immune homeostasis play an important role in the development and progression of DKD [7,8,9]. As the innate mediators of type 2 immunity, ILC2s have been focused extensively [10]. ILC2s can act as a bridge between inherent and adaptive immunity [11]. They are the first class of cells to activate type 2 immunity and play an important role in Th1/Th2 balance [12]. ILC2s provide protective immunity toward helminth infection and are responsible for allergic inflammation, tissue repair, and metabolic homeostasis and mediate multiple types of tissue fibrosis such as intestinal fibrosis, hepatic
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