Commensal bacteria regulate thymic Aire expression

• Project/Area Number: 25860818
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Juntendo University
• Principal Investigator: NAKAJIMA Akihito 順天堂大学, 医学部, 助教 (30439294)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Aire / commensal bacteria / thymic epithelial cell / peptidoglycan / superantigen / 胸腺 / 腸内細菌 / ペプチドグリカン / スーパー抗原 / Nod1 / 樹状細胞 / migration / Treg

Outline of Final Research Achievements

Commensal bacteria are reported to function as an environmental factor to regulate intestinal inflammation and immune responses. However, it remains largely unknown whether such bacterial function exerts any effect on other immune organs distant from the intestine. In this study, the influence of commensal bacteria in the thymus was investigated using germ-free mice and Nod1-deficient mice lacking an intracellular recognition receptor for certain bacterial components. Interestingly, autoimmune regulator (Aire) expression in thymic epithelial cells (TECs) was decreased in comparison to specific pathogen-free mice and Nod1 wild-type mice, respectively. The in vitro analysis using a fetal thymus organ culture system showed that Aire expression in TECs was increased in the presence of a bacterial component or a bacterial product. These results suggest that through their products, commensal bacteria have potential to give some effect on the epithelial cells of thymus.

Research Products

• [Journal Article] 腸内細菌と胸腺の知られざる関係 (2015)
  • Author(s): 中島章人
  • Journal Title: 実験動物と環境 Volume: 23 Pages: 49-52
• [Journal Article] Commensal Bacteria Regulate Thymic Aire Expression (2014)
  • Author(s): Nakajima A, Negishi N, Tsurui H, Kadowaki-Ohtsuji N, Maeda K, Nanno M, Yamaguchi Y, Shimizu N, Yagita H, Okumura K, Habu S.
  • Journal Title: PloS One Volume: 9 Issue: 8 Pages: e105904-e105904
  • DOI: 10.1371/journal.pone.0105904
  • Peer Reviewed / Open Access
• [Journal Article] 胸腺上皮細胞におけるAireの発現と腸内共生菌 (2014)
  • Author(s): 中島章人
  • Journal Title: 臨床検疫・アレルギー科 Volume: 62 Pages: 541-545
  • NAID: 40020265830
• [Journal Article] 腸内細菌によるネガティブセレクションへの関与 (2014)
  • Author(s): 中島章人
  • Journal Title: ヤクルトバイオサイエンス研究財団 Volume: 22 Pages: 99-106
• [Presentation] Commensal bacteria regulate thymic Aire expression (2014)
  • Author(s): 4)Akihito Nakajima, Naoko Negishi, Hiromichi Tsurui, Naomi Ohtsuji-Kadowaki, Masanobu Nanno, Ko Okumura and Sonoko Habu,
  • Organizer: 日本免疫学会
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] 腸内細菌と胸腺の知られざる関係 (2014)
  • Author(s): 中島章人
  • Organizer: 第５３回日本実験動物環境研究会
  • Place of Presentation: 東京
  • Year and Date: 2014-11-29
  • Invited
• [Presentation] 腸内細菌は胸腺上皮細胞のAireの発現に影響する (2014)
  • Author(s): 中島章人
  • Organizer: 第２９回自己免疫疾患研究会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-12
  • Invited
• [Presentation] Commensal bacteria influence on thymic Aire expression (2013)
  • Author(s): Akihito Nakajima
  • Organizer: KTCC
  • Place of Presentation: 京都
• [Presentation] Commensal bacteria influence on thymic Aire expression (2013)
  • Author(s): Akihito Nakajima
  • Organizer: The 15th international congress of immunology
  • Place of Presentation: ミラノ
• [Presentation] Commensal bacteria influence on thymic Aire expression (2013)
  • Author(s): Akihito Nakajima
  • Organizer: 第３７回日本免疫学会
  • Place of Presentation: 幕張