Role and mechanism of RhoF-mediated Th17 polarization in development of acute pancreatitis.

Objective To investigate the role and mechanism of Rho-related GTP-binding protein F (RhoF)-mediated Th17 polarization in the development of severe acute pancreatitis (SAP). Methods RhoF transgenic mice were randomly divided into control group (n = 10), SAP group (n = 10) and SAP+Y-27632 group (n = 10), and WT mice were randomly divided into control group (n = 10), SAP group (n = 10) and SAP+Y-27632 group (n = 10). SAP models were established in all groups except the control group. The SAP+Y-27632 group was infused with Y-27632 via tail vein after model establishment. T cells in mouse blood samples were isolated for RhoF, p-MYPT1 protein detection and ROCK activity determination, and the percentage of lymphoid CD4+T cells producing IL-17 was analyzed by flow cytometry. Results The expression of RhoF and p-MYPT1 was increased in T cells in the SAP group compared with that in the control group (P < 0.01), and the level of RhoF was closely correlated with that of p-MYPT1 (P = 0.018). The expression of RhoF protein level in T cells of mice in the RhoF group increased by approximately 30% compared to that in the WT group, and the level of spontaneous IL-17 production by CD4+ T cells was significantly increased (P = 0.003). Compared with WT mice, the histological score of pancreatic injury, the expression of RhoF and p-MYPT1 in T cells, the number of IL-17+ T cells and serum IL-17 level in RhoF transgenic mice were significantly increased (P < 0.05). The histological score, RhoF and p-MYPT1 expression of T cells, IL-17+ T cell numbers and serum IL-17 level were significantly lower in the SAP+Y-27632 group than those in the SAP group (P < 0.05). Conclusion RhoF/ROCK signaling pathway-mediated polarization of Th17 cells is involved in the pathogenesis of SAP. [ABSTRACT FROM AUTHOR]