Ursolic acid inhibits Th17 cell differentiation via STAT3/RORγt pathway and suppresses Schwann cell-mediated Th17 cell migration by reducing CXCL9/10 expression

• Published in: Innate immunity (London, England) England), 2022-07, Vol.28 (5), p.155-163
• Main Authors: Xu, Hua, Yu, Ai-ling, Zhao, Da-peng, Meng, Guang-yuan, Wang, Ling, Shan, Min, Hu, Nai-xia, Liu, Yun-lin
• Format: Article
• Language: English
• Subjects: Animals; CCL20 protein; CCR6 protein; CD4 antigen; Cell adhesion & migration; Cell differentiation; Cell Differentiation - drug effects; Cell migration; Cell Movement - drug effects; Chemokine CXCL10 - biosynthesis; Chemokine CXCL10 - metabolism; Chemokine CXCL9 - biosynthesis; Chemokine CXCL9 - metabolism; Chemokines; CXCR3 protein; Flow cytometry; Helper cells; Lipopolysaccharides; Lymphocytes T; Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism; Original; Peripheral blood; Rats; Schwann Cells - cytology; Schwann Cells - drug effects; Schwann Cells - metabolism; Stat3 protein; STAT3 Transcription Factor - metabolism; Th17 Cells - cytology; Th17 Cells - drug effects; Th17 Cells - metabolism; Triterpenes - pharmacology; Ursolic Acid; γ-Interferon
• ISSN: 1753-4259; 1753-4267
• DOI: 10.1177/17534259221094559

Th17 cells represent important immune cells. Ursolic acid (UA) can regulate immune cell activities. This study was aimed to explore the effects of UA on Th17 cell differentiation and Schwann cell(SCs)-mediated migration and the potential mechanism. Naïve CD4+ T cells were isolated from rat peripheral blood, induced for Th17 cell differentiation, and treated with UA. The proportion of Th17 cells was detected by flow cytometry assay. SCs were co-cultured with Th17 cells. Th17 cell migration was detected by Transwell assay. The molecule expression was determined by Western blot and qRT-PCR. UA inhibited the Th17 cell differentiation and suppressed the STAT3/RORγt pathway. STAT3 overexpression up-regulated p-STAT3 and RORγt expression and promoted Th17 cell differentiation under the UA treatment. In LPS- and IFN-γ-stimulated-SCs, UA suppressed the expression of chemokines CXCL9/10, but had no significant effect of CCL20 expression. The expression CXCL9/10 receptor CXCR3 was higher in Th17 cells than that in Treg cells, while the expression CCL20 receptor CCR6 was lower in Th17 cells than that in Treg cells. UA, anti-CXCR3, and anti-CCR6 treatment inhibited SCs-mediated Th17 cell migration, and anti-CXCR3 exerted stronger inhibitory effect than Anti-CCR6. UA inhibited Th17 cell differentiation through STAT3/RORγt pathway and suppressed Th17 cell migration through down-regulating CXCL9/10 expression in SCs.