Th2Cells Play A Principal Role In The Progress Of Renal Fibrosis

ObjectiveTo investigate the role of the subtypes of the CD4+T lymphocytes in the progress ofrenal fibrosis, which would provide a new approach forthe prevention and treatmentof renal fibrosis.MethodsWild type BALB/c mice and BALB/c Nu/Nu mice were applied in this study.Mouse renal fibrosis was induced by unilateral ureteral obstruction (UUO). BALB/cNu/Nu mice were reconstituted with polarized Th1or Th2cells by tail vein injection,andwere randomly divided into four groups:(A)sham group,(B) PBS+UUO group,(C) Th1reconstitution+UUO group,(D) Th2reconstitution+UUO group. Micewere sacrificed on days3,7and14after UUO operations. Then the subtypes ofCD4+T lymphocytes from spleens were isolated and analyzed by flow cytometry. Thekidney tissues were stained with HE staining, masson staining, andimmunohistochemistry to show the infiltration of inflammatory cell and the extent ofrenal fibrosis in different groups. The mRNA expressions of fibronectin, TGF-β, CollagenⅠinkidneys and transcriptional factors were analyzed by quantitativereal-time PCR. The cytokines were examined by ELISA.ResultsOur results demonstrated that in the process of UUO-induced renal fibrosis, theratios of Th2/Th1increased with time gone. The percentages of Th1cells werehighest on day3after UUO and then decreased. Meanwhile Th2cells increased andwere predominant on day14after UUO. But there were no obvious changes of Th17and Treg cells percentages during this process. Results also have shown thatTh2-reconstituted mice developed renal fibrosis easier than Th1-reconstituted micemanifested by interstitial expansion and collagen deposition, higher expression ofα-SMA and Vimentin and increased expression of fibronectin, TGF-β and collagen I.We also found that CD4+T cells from Th1-reconstitued mice tended to secret IL-4and IL-13Th2-like cytokines.ConclusionContrast the change of the percentage of each subtype of the CD4+T lymphocytesafter the UUO operation of wild type BALB/c mice, it is obviously that Th2cells playa major role in the progress of renal fibrosis. After Th1/Th2cells immunereconstitution and UUO operation, Th2cells immune reconstitution group showedmore interstitial fibrosis, and Th1cell may differentiate into Th2cell, which furtherprove the principal role of Th2cells.In conclusion, our study gave the first directevidence that Th2cells play the pivotal role in UUO-induced renal fibrosis. Inhibitionof CD4+T lymphocytes differentiation to Th2would be a potential therapeuticintervention to prevent renal fibrosis.