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Bone marrow-mesenchymal stem cells are a major source of interleukin-7 and sustain colitis by forming the niche for colitogenic CD4 memory T cells.

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  • معلومة اضافية
    • NAICS/Industry Codes:
      112990 All Other Animal Production
    • Abstract:
      Objective: Interleukin (IL)-7 is mainly produced in bone marrow (BM) that forms the niche for B cells. We previously demonstrated that BM also retains pathogenic memory CD4 T cells in murine models of inflammatory bowel disease (IBD). However, it remains unknown whether BM-derived IL-7 is sufficient for the development of IBD and which cells form the niche for colitogenic memory CD4 T cells in BM. Design: To address these questions, we developed mice in which IL-7 expression was specific for BM, and identified colitis-associated IL-7-expressing mesenchymal stem cells (MSC) in the BM. Results: IL-7-/-×RAG-1-/- mice injected with BM cells from IL-7+/+×RAG-1-/- mice, but not from IL-7-/-×RAG-1-/- mice, expressed IL-7 in BM, but not in their colon, and developed colitis when injected with CD4+CD45RBhigh T cells. Cultured BM MSC stably expressed a higher level of IL-7 than that of primary BM cells. IL-7-sufficient, but not IL-7-deficient, BM MSC supported upregulation of Bcl-2 in, and homeostatic proliferation of, colitogenic memory CD4 T cells in vitro. Notably, IL-7-/-×RAG-1-/- mice transplanted with IL-7-sufficient, but not IL-7-deficient, BM MSC expressed IL-7 in BM, but not in their colon, and developed colitis when transplanted withCD4+CD45RBhigh T cells. Conclusions: We demonstrate for the first time that BM MSC are a major source of IL-7 and play a pathological role in IBD by forming the niche for colitogenic CD4 memory T cells in BM. [ABSTRACT FROM AUTHOR]
    • Abstract:
      Copyright of Gut is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
    • Author Affiliations:
      1Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
      2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
    • ISSN:
      0017-5749
    • Accession Number:
      10.1136/gutjnl-2012-302029
    • Accession Number:
      88924814
  • Citations
    • ABNT:
      NEMOTO, Y. et al. Bone marrow-mesenchymal stem cells are a major source of interleukin-7 and sustain colitis by forming the niche for colitogenic CD4 memory T cells. Gut, [s. l.], v. 62, n. 8, p. 1142–1152, 2013. DOI 10.1136/gutjnl-2012-302029. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=asn&AN=88924814&custid=s8280428. Acesso em: 26 maio. 2020.
    • AMA:
      Nemoto Y, Kanai T, Takahara M, et al. Bone marrow-mesenchymal stem cells are a major source of interleukin-7 and sustain colitis by forming the niche for colitogenic CD4 memory T cells. Gut. 2013;62(8):1142-1152. doi:10.1136/gutjnl-2012-302029.
    • APA:
      Nemoto, Y., Kanai, T., Takahara, M., Oshima, S., Nakamura, T., Okamoto, R., Tsuchiya, K., & Watanabe, M. (2013). Bone marrow-mesenchymal stem cells are a major source of interleukin-7 and sustain colitis by forming the niche for colitogenic CD4 memory T cells. Gut, 62(8), 1142–1152. https://doi.org/10.1136/gutjnl-2012-302029
    • Chicago/Turabian: Author-Date:
      Nemoto, Yasuhiro, Takanori Kanai, Masahiro Takahara, Shigeru Oshima, Tetsuya Nakamura, Ryuichi Okamoto, Kiichiro Tsuchiya, and Mamoru Watanabe. 2013. “Bone Marrow-Mesenchymal Stem Cells Are a Major Source of Interleukin-7 and Sustain Colitis by Forming the Niche for Colitogenic CD4 Memory T Cells.” Gut 62 (8): 1142–52. doi:10.1136/gutjnl-2012-302029.
    • Harvard:
      Nemoto, Y. et al. (2013) ‘Bone marrow-mesenchymal stem cells are a major source of interleukin-7 and sustain colitis by forming the niche for colitogenic CD4 memory T cells’, Gut, 62(8), pp. 1142–1152. doi: 10.1136/gutjnl-2012-302029.
    • Harvard: Australian:
      Nemoto, Y, Kanai, T, Takahara, M, Oshima, S, Nakamura, T, Okamoto, R, Tsuchiya, K & Watanabe, M 2013, ‘Bone marrow-mesenchymal stem cells are a major source of interleukin-7 and sustain colitis by forming the niche for colitogenic CD4 memory T cells’, Gut, vol. 62, no. 8, pp. 1142–1152, viewed 26 May 2020, .
    • MLA:
      Nemoto, Yasuhiro, et al. “Bone Marrow-Mesenchymal Stem Cells Are a Major Source of Interleukin-7 and Sustain Colitis by Forming the Niche for Colitogenic CD4 Memory T Cells.” Gut, vol. 62, no. 8, Aug. 2013, pp. 1142–1152. EBSCOhost, doi:10.1136/gutjnl-2012-302029.
    • Chicago/Turabian: Humanities:
      Nemoto, Yasuhiro, Takanori Kanai, Masahiro Takahara, Shigeru Oshima, Tetsuya Nakamura, Ryuichi Okamoto, Kiichiro Tsuchiya, and Mamoru Watanabe. “Bone Marrow-Mesenchymal Stem Cells Are a Major Source of Interleukin-7 and Sustain Colitis by Forming the Niche for Colitogenic CD4 Memory T Cells.” Gut 62, no. 8 (August 2013): 1142–52. doi:10.1136/gutjnl-2012-302029.
    • Vancouver/ICMJE:
      Nemoto Y, Kanai T, Takahara M, Oshima S, Nakamura T, Okamoto R, et al. Bone marrow-mesenchymal stem cells are a major source of interleukin-7 and sustain colitis by forming the niche for colitogenic CD4 memory T cells. Gut [Internet]. 2013 Aug [cited 2020 May 26];62(8):1142–52. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=asn&AN=88924814&custid=s8280428