|Mucosal administration of alpha-fodrin inhibits experimental Sjogren′s syndrome autoimmunity|
|He, Jing; Zhao, Jinxia; Li, Zhanguo|
|刊名||ARTHRITIS RESEARCH & THERAPY|
|WOS标题词||Science & Technology|
|关键词[WOS]||DENDRITIC CELLS ; ORAL TOLERANCE ; NOD MOUSE ; AUTOANTIBODIES ; AUTOANTIGEN ; MICE ; ANTIBODIES ; MECHANISMS ; PEPTIDE ; NASAL|
Introduction alpha-Fodrin is an autoantigen in Sjogren′s syndrome. We hypothesized that mucosal administration of alpha-fodrin might prevent the disease.
Methods Four-week-old NOD mice were immunized (intranasal) with a 1 mu g or 10 mu g dose of alpha-fodrin every other day. PBS 10 mu l/dose and Glutathione transferase (GST 10 mu g/dose (control mice) were intranasally administrated by the same procedure. The salivary flow was maintained in immunized animals. The animals were analyzed for the presence of anti-Sjogren′s syndrome A, anti-Sjogren′s syndrome B, rheumatoid factor and antinuclear, anti-alpha-fodrin, and anti-type 3 muscarinic acetylcholine receptor polypeptide (anti-M3RP) by immunofluorescence or ELISA. The cytokines IFN gamma and IL-10 were measured by ELISA. Salivary glands were examined by H& E staining and immunohistochemical analysis. The water-volume intake was calculated for each group. The induction of regulatory T cells was assessed by fluorescence-activated cell sorting analysis for the frequency of Foxp3(+) cells among peripheral CD4(+) CD25(+) T cells.
Results The appearance of anti-alpha-fodrin and anti-M3RP antibodies was delayed in mice immunized with alpha-fodrin. The titers of anti-alpha-fodrin and anti-M3RP antibodies were lower in immunized mice (P < 0.05), but there was no significant difference between the low-dose or high-dose immunization groups. Five out of eight mice in the GST group, five of eight mice in the PBS group, two of eight mice in the alpha-fodrin 1 mu g/dose group, and three out of eight mice in the alpha-fodrin 10 mu g/dose were positive for antinuclear antibodies. The levels of serum IFN gamma in mice immunized with 1 mu g/dose or 10 mu g/dose alpha-fodrin,with PBS, and with GST were 41.9 +/- 16.2 pg/ml, 37.1 +/- 15.4 pg/ml, 86.8 +/- 17.8 pg/ml and 71.6 +/- 11.1 pg/ml, respectively, while we found no difference in the levels of serum IL-10 among the groups. The number of Foxp3(+) CD4(+) CD25(+) regulatory T cells was higher in the alpha-fodrin groups compared with the PBS and GST control groups (P < 0.05). Lymphocytic infiltration and expression of alpha-fodrin in the salivary glands was decreased in alpha-fodrin-treated groups. The fluid intake of mice in the 1 mu g/dose alpha-fodrin, 10 mu g/dose mu-fodrin, PBS, and GST groups was 39.2 +/- 2.1 ml, 40.4 +/- 2.5 ml, 49.3 +/- 3.1 ml and 51.6 +/- 2.8 ml, respectively.
Conclusion Mucosal administration of alpha-fodrin effectively inhibited the progression of experimental Sjogren′s syndrome autoimmunity.
|作者单位||Peking Univ, Peoples Hosp, Dept Rheumatol Immunol, Sch Med, Beijing 100044, Peoples R China|
|He, Jing,Zhao, Jinxia,Li, Zhanguo. Mucosal administration of alpha-fodrin inhibits experimental Sjogren′s syndrome autoimmunity[J]. ARTHRITIS RESEARCH & THERAPY,2008,10(2).|
|APA||He, Jing,Zhao, Jinxia,&Li, Zhanguo.(2008).Mucosal administration of alpha-fodrin inhibits experimental Sjogren′s syndrome autoimmunity.ARTHRITIS RESEARCH & THERAPY,10(2).|
|MLA||He, Jing,et al."Mucosal administration of alpha-fodrin inhibits experimental Sjogren′s syndrome autoimmunity".ARTHRITIS RESEARCH & THERAPY 10.2(2008).|