Kuijieling regulates the differentiation of Treg and Th17 cells to ameliorate experimental colitis in rats

Abstract

Background: Regulatory T (Treg) cells and T helper 17 (Th17) cells play crucial roles in ulcerative colitis (UC). Kuijieling (KJL) is an effective Chinese medicine formula for treating UC in clinic. Kuijieling has shown remedy effect on the imbalance between Treg and Th17 cells. This study aimed to further reveal the exact underlying mechanism of how Kuijieling regulates the differentiation of Treg and Th17 cells in the treatment of UC.

Methods: Colitis was induced by trinitrobenzene sulfonic acid in rats and treated by KJL. Pathological injury was evaluated by HE staining and pathological score. Transforming growth factor-β1 (TGF-β1), interleukin(IL)-2, IL-6, IL-10, IL-17, IL-23 and IL-21 in plasma were assayed by ELISA. Forkhead box P3 (Foxp3), signal transducer and activator of transcription (STAT) 5 expressed in colon mucosa were measured by western blot. Immunohistochemistry was employed for quantifying retinoic acid-related orphan receptor γt (RORγt) and STAT3 in colon. RT-PCR was used to analyze the expression of IL-2, IL-17, IL-23, IL-21 mRNA in colon.

Results: After the administration of KJL, pathological injury in colon mucosa was reduced and histological score was decreased, transforming growth factor-β1 (TGF-β1), interleukin(IL)-2, IL-10 in blood and Foxp3, STAT5, IL-2 in colon increased significantly, IL-6, IL-23, IL-17, IL-21 in blood and RORγt, STAT3, IL-23, IL-17, IL-21 in colon decreased. Our result showed that KJL regulates the related cytokines and transcription factors to promote Treg cells and suppress Th17 cells.

Conclusion: KJL restores the balance between Treg and Th17 cells through regulating the differentiation of them, therefore contributes to the treatment of UC.

Keywords: Atractylodes macrocephala; Chinese medicine; Forkhead box P3; Ilex rotunda Thunb; Inflammatory bowel disease; Interleukin-10; Interleukin-17; Interleukin-2; Interleukin-21; Interleukin-23; Interleukin-6; Kuijieling; Paeonia lactiflora pall; Regulatory T cell; Retinoic acid-related orphan receptor γt; Signal transducer and activator of transcription 3; Signal transducer and activator of transcription 5; T helper-17 cell; Transforming growth factor-β1 (TGF-β1); Ulcerative colitis; Whitmania pigra Whitman; radix Glycyrrhizae Preparata.