Suppression of GPI-induced arthritis by oral administration of transgenic rice seeds expressing altered peptide ligands

Abstract

Objective: To investigate the effects and mechanisms of transgenic rice seeds expressing the altered peptide ligand (APL) of human glucose-6-phosphate-isomerase (hGPI_325-339) in mice model of GPI induced arthritis (GIA). Methods: We generated transgenic rice expressing APL12 which was analog peptide of hGPI_325-339. The transgenic rice seeds were orally administered prophylactically before the induction of GIA. The severity of arthritis and titers of serum anti-GPI antibodies were evaluated. We examined IL-17 production from splenocytes and inguinal lymph node (iLN) and mesenteric lymph nodes (mLN) cells and analyzed the expression levels of functional molecules from splenocytes and iLN cells. Results: Prophylactic treatment of GIA mice with APL12 transgenic rice seeds (APL12-TG) significantly improved the severity of arthritis, histopathological arthritis scores, and decreased titers of serum anti-GPI antibodies, BAFF mRNA in iLN cells, IL-17 production in splenocytes and iLN cells compared with non-transgenic rice-treated mice. APL12-TG-treated GIA mice showed upregulation of Foxp3 and GITR protein in CD4⁺CD25⁺ cells in the spleen. Conclusion: APL12-TG improved the severity of GIA through a decrease in production of IL-17 and anti-GPI antibodies via upregulation of Foxp3 and GITR expression on regulatory T cells in spleen.