Redox regulation of a new autoimmune mouse model, glucose-6-phosphate isomerase peptide induced arthritis in mice (BA12P.108)

Abstract

Abstract Human glucose-6-phosphate isomerase (hG6PI) peptide-induced arthritis is established by immunizing C57Bl/6N.Q (B6N.Q) mice with single hGPI325-339 peptide emulsified in complete freund’s adjuvant. Immunized B6N.Q mice start to develop arthritis on day 10-12, reach to the peak value of severity on day 14-20 and then recover during the next 7-10 days. This peptide-induced arthritis mouse model represents an acute arthritic disease progression. By taking advantage of μMT mice (B cell deficient) and TCRβ-/- (T cell deficient) mice, we have demonstrated that this peptide-induced arthritis is T cell- and B cell- dependent. In addition, by using Ncf1 mutant mice, which are lack of oxidative burst, we have found that reduced reactive oxygen specifics aggravate and prolong the peptide-induced arthritis. Phenotypic analysis results show that increased frequency and absolute numbers of Th17 cells, accompanied by significant increased CD11b+cells, are observed in Ncf1 mutant mice comparing with wild-type mice; moreover, IL-17 levels were dramatically increased in isolated splenic cells or lymph nodes cells from immunized Ncf1 mutant mice when restimulated with hGPI325-339 peptide. Moreover, in vitro experiments suggest that APCs from Ncf1 mutant mice show higher capability to present hGPI325-339 peptide to stimulate hGPI325-339 peptide specific T cell hybridoma, which suggest that enhanced antigen-presentation capability may aggravate the arthritic disease in Ncf1 mutant mice.