2019 Fiscal Year Final Research Report

Establishment of an analytical workflow to elucidate the molecular biology of the pathogenesis of gastrointestinal diseases in neonates

Research Project

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Project/Area Number	17H04235
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	Embryonic/Neonatal medicine
Research Institution	Saitama Medical University (2019) Nagoya University (2017-2018)
Principal Investigator	Tanaka Yujiro 埼玉医科大学, 医学部, 教授 (90382928)
Co-Investigator(Kenkyū-buntansha)	澤新一郎九州大学, 生体防御医学研究所, 教授 (80611756) 大島一夫名古屋大学, 医学部附属病院, 医員 (20764880) 田井中貴久名古屋大学, 医学部附属病院, 病院講師 (30378195) 内田広夫名古屋大学, 医学系研究科, 教授 (40275699) 住田亙名古屋大学, 医学部附属病院, 病院講師 (70437044) 城田千代栄名古屋大学, 医学部附属病院, 講師 (20378194) 檜顕成名古屋大学, 医学系研究科, 特任教授 (90383257)
Project Period (FY)	2017-04-01 – 2020-03-31
Keywords	新生児腸管免疫細胞 / 3型自然リンパ球 / 壊死性腸炎 / Single-cell RNA sequence
Outline of Final Research Achievements	Lymphocytes of 71 resected human bowels were examined using flow cytometry. Type 3 innate lymphoid cells (ILC3), which is known to regulate bowel immunity, was detected in all specimens. However, the percentage of ILC3 was not constant according to the condition of patients, e.g. gestational week and disease. Studying the bowel specimens of emergency laparotomy in human neonates, we also investigated the differences in gene expression between necrotizing enteritis and non-necrotic intestinal perforation. We studied the gene expression on a cell-by-cell basis of about 10,000 cells per each case, so we can assess what cells were specifically showing abnormal responses. To date, there have been no reports of gene expression analysis on a cell-by-cell basis. In necrotizing enteritis, T cells were dominant and pathways concerning inflammation, e.g. MYC targets, mTORC1 signaling, TNFA signaling were activated. In non-necrotic intestinal perforation, innate monocytic cells were the major.
Free Research Field	小児外科学
Academic Significance and Societal Importance of the Research Achievements	新生児にとって致死的になりうる壊死性腸炎と、壊死性腸炎ほどに致死的ではない限局性腸穿孔を比べて、ひとつひとつの腸管細胞における遺伝子発現の違いを調べた。結果として、壊死性腸炎では、炎症が起きる際に認める多くの遺伝子発現が明らかに高度だった。この結果について、さらに分析を進めることで、予後不良な新生児壊死性腸炎の原因追及や、予防法、新規治療法の開発に発展させられる可能性がある。これによって命が助かる子供や、その後の人生の不自由が減る子供がでてくると期待している。また、新生児壊死性腸炎は主に低出生体重児の新生児期にのみ起こる疾患であり、ヒト腸管の免疫機能の発達を解明するてがかりになる可能性がある。