Group 2 Innate Lymphoid Cells Participate in Renal Fibrosis in Diabetic Kidney Disease Partly via TGF-1 Signal Pathway.

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-1 (TGF-1), fibronectin (FN), collagen1, IL-4R, and IL-13R1 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 ( < 0.05). The expression of TGF-1, FN, and collagen1 was significantly upregulated in HK-2 cells induced by IL-4 or IL-13 ( < 0.05). Moreover, the IL-4R and IL-13R1 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 ( > 0.05). However, compared with high-glucose stimulation alone, the expression of TGF-1, FN, and collagen1 was significantly increased in HK-2 cells induced by high glucose combined with IL-4 or IL-13 ( < 0.05).

CONCLUSIONS

ILC2s may participate in renal fibrosis in DKD partly via TGF-1 signal pathway.