Total glucosides of paeony inhibits the differentiation and migration of intestinal mucosal immune Th17 cells in Sjogren’s syndrome mice
Year: 2026
Type: article
Abstract: Background Sjogren’s syndrome (SS) is marked by exocrine-gland infiltration and Th17-driven inflammation; low-bioavailability Total glucosides of paeony (TGP) shows efficacy yet unclear mechanisms. Purpose To investigate the role of intestinal mucosal immunity in SS pathogenesis and the effect of TGP on the differentiation and migration of Th17 in intestinal mucosal immunity. Methods SS was induced in Peyer’s patches (PPs)/mesenteric lymph nodes (MLNs)-deficient mice. Saliva/tear flow, gland histopathology, Th17-related cytokine mRNA and blood Th17 were assessed. Established SS mice were treated with 6-week TGP. Flow cytometry/RT-qPCR evaluated CD4 + T cell proliferation, dendritic cell (DC) activation, and Th17 differentiation, migration and homing in intestinal mucosal immunity, blood, exocrine glands. Immunofluorescence observed the migration of in vitro -polarized, CFSE-labeled Th17 cells to the submandibular glands (SMG). In vitro , naive CD4 + T cells from PPs/MLNs were cultured with cytokines or LPS-activated bone marrow DCs (BMDCs) to induce Th17 differentiation, with TGP incubated. CD4 + T cell proliferation, Th17 proportion and cytokine mRNA was determined. Results PPs- or MLNs-deficient SS mice showed no significant increase in SS manifestations or Th17 markers. In vivo , TGP inhibited CD4 + T cell proliferation, Th17 differentiation and DC activation/migration, blocking Th17 gland entry and gut homing by down-regulating CCR6/CCL20, CCR9/CCL25 and α4β7/MAdCAM-1 axis. Immunofluorescence results also clearly demonstrated that TGP significantly inhibited the migration of intestinal mucosa-derived Th17 cells to the SMG. In vitro , TGP left BMDC activation intact but sharply suppressed BMDC-driven Th17 differentiation by reducing proliferation and Th17 cytokines. Conclusion TGP attenuates SS inflammation by inhibiting Th17 differentiation and migration from intestinal mucosal immunity to exocrine glands and their homing to intestinal mucosa.
Source: Frontiers in Immunology
Authors: Ge Liu, Jing Liu, Xingyu Yan, Teng Chu, Yue Wu, Weirong Fang
Institution: China Pharmaceutical University
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
Award: G8911750099
OpenAlex ID: W7221703223
