The establishment of antigen specific therapy for Sjogren syndrome

• Project/Area Number: 26870078
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathobiological dentistry/Dental radiology; Collagenous pathology/Allergology
• Research Institution: University of Tsukuba
• Principal Investigator: Asashima Hiromitsu 筑波大学, 医学医療系, 講師 (50708485)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 抗原特異的治療法 / シェーグレン症候群 / アナジー

Outline of Final Research Achievements

Rag1-/- mice transferred with splenocytes of M3 muscarinic acetylcoline receptor (M3R)-/- mice immunized with M3R peptides mixture (N-terminal regions; N1, N2, N3, and three extracellular loops; 1st, 2nd, 3rd) developed sialadenitis like Sjogren’s syndrome (SS) (M3R induced sialadenitis; MIS). we confirmed that in MIS, M3R reactive CD4+ T cells were indispensable and the T cell epitopes were both N1 and 1st regions. Besides, altered peptide ligands (APLs) , substituted in amino acid residues at TCR contact sites, of N1 peptide can regulate the T cell activation by inducing anergy, leading to the suppression of sialadenitis in vivo. This research was reported by the journal of 'Arthritis and Rheumatology'.

Research Products

• [Journal Article] The anergy induction of M3 muscarinic acetylcholine receptor-reactive CD4+ T cells suppresses experimental sialadenitis-like Sjogren's syndrome. (2015)
  • Author(s): Asashima H, Tsuboi H, Takahashi H, Hirota T, Iizuka M, Kondo Y, Matsui M, Matsumoto I, Sumida T.
  • Journal Title: Arthritis and Rheumatology Volume: 67 Issue: 8 Pages: 2213-2225
  • DOI: 10.1002/art.39163
  • Peer Reviewed
• [Presentation] APL投与によるM3R誘導自己免疫性唾液腺炎の抗原特異的制御 (2015)
  • Author(s): 浅島弘充, 坪井洋人, 飯塚麻菜, 高橋広行, 廣田智哉, 近藤裕也, 松本功, 住田孝之
  • Organizer: 第24回日本シェーグレン症候群学会学術集会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-09-18
• [Presentation] The anergy induction of M3R reactive CD4+ T cells suppresses experimental sialadenitis like Sjogren’s syndrome in vivo (2015)
  • Author(s): H. Asashima, H. Tsuboi, H. Takahashi, T. Hirota, M. Iizuka, Y. Kondo, I. Matsumoto and T. Sumida.
  • Organizer: The 13th International Symposium on Sjogren’s syndrome
  • Place of Presentation: Radisson Blu Royal Hotel, Bryggen Bergen
  • Year and Date: 2015-05-19
  • Int'l Joint Research
• [Presentation] The anergy induction of M3R reactive CD4+ T cells suppresses experimental sialadenitis like Sjogren’s syndrome in vivo (2015)
  • Author(s): Hiromitsu Asashima, Hiroto Tsuboi, Hiroyuki Takahashi, Tomoya Hirota, Mana Iizuka, Yuya Kondo, Isao Matsumoto and Takayuki Sumida.
  • Organizer: 第59回日本リウマチ学会総会学術集会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-04-23
• [Presentation] The suppressive ability of altered peptides ligands to M3R induced autoimmune sialadenitis (2014)
  • Author(s): Hiromitsu Asashima, Hiroto Tsuboi, Hiroyuki Takahashi, Chihiro Hagiya, Tomoya Hirota, Mana Iizuka, Yuya Kondo, Isao Matsumoto, Takayuki Sumida
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] APL投与によるM3R誘導自己免疫性唾液腺炎の抗原特異的制御 (2014)
  • Author(s): 浅島弘充、坪井洋人、飯塚麻菜、高橋広行、萩谷千裕、廣田智哉、近藤裕也、松本功、住田孝之
  • Organizer: 第23回日本シェーグレン症候群学会学術集会
  • Place of Presentation: ホテルニュー長崎
  • Year and Date: 2014-09-12 – 2014-09-13
• [Presentation] The suppressive ability of altered peptide ligands to M3R induced autoimmune sialoadenitis in vivo (2014)
  • Author(s): Hiromitsu Asashima, Hiroto Tsuboi, Mana Iizuka, Chihiro Hagiya, Tomoya Hirota, Yuya Kondo, Isao Matsumoto and Takayuki Sumida
  • Organizer: 2014 Annual European Congress of Rheumatology in Paris
  • Place of Presentation: France, Paris
  • Year and Date: 2014-06-11 – 2014-06-14
• [Presentation] The suppressive ability of altered peptides ligands to M3R induced autoimmune sialadenitis (2014)
  • Author(s): Hiromitsu Asashima, Hiroto Tsuboi, Mana Iizuka, Chihiro Hagiya, Tomoya Hirota, Yuya Kondo, Isao Matsumoto, Takayuki Sumida
  • Organizer: 第58回日本リウマチ学会学術集会
  • Place of Presentation: グランドプリンスホテル新高輪
  • Year and Date: 2014-04-24 – 2014-04-26