Molecular mechanism of Sjogren's syndrome

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17591027
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: University of Tsukuba
• Principal Investigator: SUMIDA Takayuki University of Tsukuba, Graduate School of Comprehensive Human Sciences, Professor, 大学院人間総合科学研究科, 教授 (00183054)
• Project Period (FY): 2005 – 2006
• Keywords: Sjogren's syndrome / autoreactive T cell / T cell epitope / analogue peptide / Muscalinic acetylcholine receptor / autoantigen / antigen specific regulation / mouse model

Research Abstract

1.Regulation of SS by analogue peptide of T cell epitopes
To propose the new therapeutic strategies using analogue peptide of T cell epitopes, we focused on muscarinic acetylcholine receptor (M3R). The second extra-cellular domain of M3R is the most important region for intra-cellular signaling. Thus, we analyzed T cell epitopes of the second extra-cellular domain of M3R, screened the analogue peptides of T cell epitopes, and establish an antigen-specific regulation of SS using analogue peptides. 1) We clarified VPPGECFIQFLSEPT (AA215-229) was T cell epitope of M3R in HLA-DR B1*0901 positive patients with SS. 2) We selected two of candidates for analogue T cell epitopes were VPPGECFKQFLSEPT and VPPGECFIAFLSEPT. 3)We established mouse model for SS by the immunization of M3R peptides plus CFA.
2.Gene analysis of susceptibility genes in patients with SS
To elucidate susceptibility genes in patients with SS, we analyzed highly expressed genes in labial salivary glands (LSGs) using cDNA microarray. We screened STAT1 gene as a candidate for over-expressed genes. The Tyr701 and Ser727 were phosphorylated and were mainly expressed in LSGs epithelial cells of SS. Moreover, apoptotic genes such as Fas, IP-10, and RF-1 were highly expressed. These results suggest that over-expression of STAT1 might be associated to the apoptosis of LSG epithelial cells in patients with SS.

Research Products

• [Journal Article] Overexpression of phosphorylated STAT-1α in the labial salivary glands from patients with Sjogren's syndrome. (2006)
  • Author(s): Wakamatsu, E., Matsumoto, I., Naito, Y., Goto, D., Mamura, M., Ito, S., Tsutsumi, A., Sumida.T.
  • Journal Title: Arthritis Rheum. 54 Pages: 3476-3484
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Altered peptide ligands regulate muscarinic acetylcholine receptor reactive T cells from patients with Sjogren's syndrome. (2006)
  • Author(s): Naito, Y., Matsumoto, I., Wakamatsu, E., Goto, D., Ito, S., Tsutsumi, A., Sumida, T.
  • Journal Title: Ann. Rheum. Dis. 65 Pages: 269-271
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Characterization of Th1/Th2 type, glusoce-6-phoshate isomerase reactive T cells in the generation of rheumatoid arthritis. (2006)
  • Author(s): Kori, Y., Matsumoto, I., Zhang, H., Yasukochi, T., Hayashi, T., Iwanami, K., Goto, D., Ito, S., Tsutsumi, A., Sumida, T.
  • Journal Title: Ann. Rheum. Dis. 65 Pages: 968-969
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Overexpression of phosphorylated STAT-1 α in the labial salivary glands from patients with Sjogren' s syndrome. (2006)
  • Author(s): Wakamatsu, E., Matsumoto, I., Naito, Y., Goto, D., Mamura, M., Ito, S., Tsutsumi, A., Sumida, T.
  • Journal Title: Arthritis Rheum. 54 Pages: 3476-3484
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Altered peptide ligands regulate muscarinic acetylcholine receptor reactive T cells from patients with Sjogren' s syndrome. (2006)
  • Author(s): Naito, Y., Matsumoto, I., Wakamatsu, E., Goto, D., Ito, S., Tsutsumi, A., Sumida, T.
  • Journal Title: Ann.Rheum.Dis. 65 Pages: 269-271
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Characterization of Th1/Th2 type, glusoce-6-phoshate isomerase reactive T cells in the generation of rheumatoid arthritis. (2006)
  • Author(s): Kori, Y., Matsumoto, I., Zhang, H., Yasukochi, T., Hayashi, T., Iwanami, K., Goto, D., Ito, S., Tsutsumi, A., Sumida, T.
  • Journal Title: Ann.Rheum.Dis. 65 Pages: 968-969
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Muscarinic acetylcholine receptor autoantibodies in patients with Sjogren's syndrome. (2005)
  • Author(s): Naito, Y., Matsumoto, I., Wakamatsu, E., Goto, D., Tsutsumi, A., Sumida.T.
  • Journal Title: Ann. Rheum. Dis 64 Pages: 510-511
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] TCRV α 14+ NKT cells function as effector T cells in collagen-induced arthritis mice. (2005)
  • Author(s): Ohnishi, Y., Tsutsumi, A., Goto, D., Itoh, S., Matsumoto, I., Taniguchi, M., Sumida, T.
  • Journal Title: Clin. Exp. Immunol. 141 Pages: 47-53
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Muscarinic acetylcholine receptor autoantibodies in patients with Sjogren' s syndrome. (2005)
  • Author(s): Naito, Y., Matsumoto, I., Wakamatsu, E., Goto, D., Tsutsumi, A., Sumida, T.
  • Journal Title: Ann.Rheum.Dis. 64 Pages: 510-511
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] TCRV α 14+ NKT cells function as effector T cells in collagen-induced arthritis mice. (2005)
  • Author(s): Ohnishi, Y., Tsutsumi, A., Goto, D., Itoh, S., Matsumoto, I., Taniguchi, M., Sumida, T.
  • Journal Title: Clin.Exp.Immunol. 141 Pages: 47-53
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] DNA microarray analysis of labial salivary glands from patients with Sjogren's syndrome.
  • Author(s): Wakamatsu, E., Nakamura, Y., Matsumoto, I., Goto, D., Ito, S., Tsutsumi, A., Sumida, T.
  • Journal Title: Ann. Rheum. Dis. (in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] DNA microarray analysis of labial salivary glands from patients with Sjogren' s syndrome.
  • Author(s): Wakamatsu, E., Nakamura, Y., Matsumoto, I., Goto, D., Ito, S., Tsutsumi, A., Sumida, T.
  • Journal Title: An.Rheum.Dis. (in press)
  • Description: 「研究成果報告書概要(欧文)」より