Peyer's patch immune cells regulates intestinal bacteria: basic research for the manipulation of intestinal bacteria by foods

• Project/Area Number: 15K07438
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Food science
• Research Institution: Dokkyo Medical University
• Principal Investigator: HASHIGUCHI Masaaki 獨協医科大学, 医学部, 准教授 (20372443)
• Research Collaborator: KOBAYASHI Ayano ; TASAKU Yumi
• Project Period (FY): 2015-10-21 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: パイエル板 / 自然リンパ球 / 腸内細菌 / IL-22 / APRIL / BAFF / IgA

Outline of Final Research Achievements

Anatomical containment of commensal bacteria in the intestinal mucosa is promoted by innate lymphoid cells (ILCs). We show that Peyer’s patch (PP) ILCs robustly produce IL-22 in the absence of exogenous stimuli. In vivo depletion of ILCs rather than T cells altered the composition of and allowed the proliferation of bacteria in PPs. Collectively, our results show that ILCs restrain commensal bacteria in the PPs.
Intestinal immunoglobulins (Igs) protect against microbes. We have investigated the roles of APRIL (TNFSF13) and BAFF (TNFSF13B) in intestinal Ig induction. PPs are, at least in part, an inductive site for Igs, including IgA. Our results demonstrate that APRIL and BAFF in vivo lowered the frequency of isotype-switched B cells in PPs. These results indicate that APRIL and BAFF paradoxically downregulate homeostatic Ig production in the intestines.

Research Products

• [Journal Article] Tumor necrosis factor superfamily member (TNFSF) 13 (APRIL) and TNFSF13B (BAFF) downregulate homeostatic immunoglobulin production in the intestines (2018)
  • Author(s): Hashiguchi, M., Kashiwakura, Y., Kanno, Y., Kojima, H., Kobata, T.
  • Journal Title: Cell. Immunol. Volume: 323 Pages: 41-48
  • DOI: 10.1016/j.cellimm.2017.10.009
  • Peer Reviewed
• [Presentation] Tumor necrosis factor superfamily member (TNFSF) 13, APRIL and TNFSF13B, BAFF downregulate homeostatic immunoglobulin production in intestines (2017)
  • Author(s): Hashiguchi, M., Kashiwakura, Y., Kojima, H., Kanno, Y., Kobata, T.
  • Organizer: 第46回日本免疫学会総会・学術集会
• [Presentation] Differences in specificity and production between IgA and IgG in Peyer’s patches (2016)
  • Author(s): Masaaki Hashiguchi, Yuji Kashiwakura, Hidefumi Kojima, Yumiko Kanno, Tetsuji Kobata
  • Organizer: 日本免疫学会学術集会
  • Place of Presentation: 沖縄コンベンションセンター (沖縄県 宜野湾市)
  • Year and Date: 2016-12-05
• [Presentation] Peyer’s patch innate lymphoid cells regulate commensal bacteria expansion (2016)
  • Author(s): Masaaki Hashiguchi, Ayano Kobayashi, Yuji Kashiwakura, Hidefumi Kojima, Yumiko Kanno, Tetsuji Kobata
  • Organizer: International Congress of Immunology 2016
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2016-08-22
  • Int'l Joint Research
• [Presentation] Peyer’s patch innate lymphoid cells regulate commensal bacteria expansion (2015)
  • Author(s): Hashiguchi Masaaki, Kashiwakura Yuji, Kojima Hidefumi, Kanno Yumiko, Kobata Tetsuji
  • Organizer: 日本免疫学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2015-11-20