論文

査読有り 国際誌
2020年2月1日

Elucidation of the Effects of a Current X-SCID Therapy on Intestinal Lymphoid Organogenesis Using an In Vivo Animal Model.

Cellular and molecular gastroenterology and hepatology
  • Tomonori Nochi
  • Shunichi Suzuki
  • Shun Ito
  • Shotaro Morita
  • Mutsumi Furukawa
  • Daiichiro Fuchimoto
  • Yoji Sasahara
  • Katsuki Usami
  • Kanae Niimi
  • Osamu Itano
  • Minoru Kitago
  • Sachiko Matsuda
  • Ayumi Matsuo
  • Yoshihisa Suyama
  • Yoshifumi Sakai
  • Guoyao Wu
  • Fuller W Bazer
  • Kouichi Watanabe
  • Akira Onishi
  • Hisashi Aso
  • 全て表示

10
1
開始ページ
83
終了ページ
100
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.jcmgh.2020.01.011

BACKGROUND & AIMS: Organ-level research using an animal model lacking Il2rg, the gene responsible for X-linked severe combined immunodeficiency (X-SCID), is clinically unavailable and would be a powerful tool to gain deeper insights into the symptoms of patients with X-SCID. METHODS: We used an X-SCID animal model, which was first established in our group by the deletion of Il2rg gene in pigs, to understand the clinical signs from multiple perspectives based on pathology, immunology, microbiology, and nutrition. We also treated the X-SCID pigs with bone marrow transplantation (BMT) for mimicking a current therapeutic treatment for patients with X-SCID and investigated the effect at the organ-level. Moreover, the results were confirmed using serum and fecal samples collected from patients with X-SCID. RESULTS: We demonstrated that X-SCID pigs completely lacked Peyer's patches (PPs) and IgA production in the small intestine, but possessed some dysfunctional intestinal T and B cells. Another novel discovery was that X-SCID pigs developed a heterogeneous intestinal microflora and possessed abnormal plasma metabolites, indicating that X-SCID could be an immune disorder that affects various in vivo functions. Importantly, the organogenesis of PPs in X-SCID pigs was not promoted by BMT. Although a few isolated lymphoid follicles developed in the small intestine of BMT-treated X-SCID pigs, there was no evidence that they contributed to IgA production and microflora formation. Consistently, most patients with X-SCID who received BMT possessed abnormal intestinal immune and microbial environments regardless of the presence of sufficient serum IgG. CONCLUSIONS: These results indicate that the current BMT therapies for patients with X-SCID may be insufficient to induce the organogenesis of intestinal lymphoid tissues that are associated with numerous functions in vivo.

リンク情報
DOI
https://doi.org/10.1016/j.jcmgh.2020.01.011
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32017983
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210612
ID情報
  • DOI : 10.1016/j.jcmgh.2020.01.011
  • PubMed ID : 32017983
  • PubMed Central 記事ID : PMC7210612

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