The mechanism of gastric MALT lymphoma formation after H. suis infection via the activation of CXCL13

Research Project

Project/Area Number	17K15684
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Bacteriology (including mycology)
Research Institution	Hokkaido University
Principal Investigator	YAMAMOTO KOJI 北海道大学, 医学研究院, 特任助教 (70608322)
Project Period (FY)	2017-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000) Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	Helicobacter suis / 胃MALTリンパ腫 / 濾胞性樹状細胞 / インターフェロンγ / インターフェロンγ受容体 / CXCL13 / IFN-γ / IFNGR / H. suis / 濾胞樹状細胞 / 細菌 / 感染症 / 粘膜免疫学
Outline of Final Research Achievements	Helicobacter suis (H. suis) infects various animals especially in pigs and humans. Interestingly, it has been reported that H. suis infection is able to induce the formation of gastric mucosa associated lymphoid tissue (MALT) lymphomas in 100% of mice. In addition, we recently reported that the formation of gastric lymphoid follicles following H. suis infection is dependence on the high expression of interferon-γ (IFN-γ) and CXC chemokine ligand 13 (CXCL13). However, the relationship between the expression of IFN-γ and the production of CXCL13 in the stomach of H. suis infected mice remains unclear. In this study, we showed that the expression of IFN-γ interacting with IFNGR on FDC produces CXCL13 through the activation of IkB-α-NF--B2 pathway.These results suggest that the interaction between IFN-γ and IFNGR is important for CXCL13 production from FDCs and is associated with gastric lymph follicle formation after H.suis infection.
Academic Significance and Societal Importance of the Research Achievements	ヘリコバクタースイス (H. suis)は、マウス胃粘膜に感染するとCXCL13と呼ばれる遺伝子が高発現しており、抗CXCL13抗体を用いると胃MALTリンパ腫発症を有意に抑制させることが明らかとなっている。よって、H. suis感染後のCXCL13の発現が胃MALTリンパ腫発症に関与していると考えられる。そこで本研究課題では、H. suis感染からどのようなメカニズムでCXCL13を産生させ、どのように胃MALTリンパ腫を発症させれいるかの解明を目的とする。これらの詳細を明らかにすることで胃MALTリンパ腫発症を抑制させる新規治療法の開発が期待される。