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CD4+VEGFR1HIGH T cell as a novel Treg subset regulates inflammatory bowel disease in lymphopenic mice

Cellular & Molecular Immunology volume 12, pages 592–603 (2015)Cite this article

Abstract

Regulatory T cells (Tregs) are a specialized subpopulation of T cells that control the immune response and thereby maintain immune system homeostasis and tolerance to self-antigens. Many subsets of CD4+ Tregs have been identified, including Foxp3+, Tr1, Th3, and Foxp3neg iT(R)35 cells. In this study, we identified a new subset of CD4+VEGFR1high Tregs that have immunosuppressive capacity. CD4+VEGFR1high T cells, which constitute approximately 1.0% of CD4+ T cells, are hyporesponsive to T-cell antigen receptor stimulation. Surface marker and FoxP3 expression analysis revealed that CD4+VEGFR1high T cells are distinct from known Tregs. CD4+VEGFR1high T cells suppressed the proliferation of CD4+CD25− T cell as efficiently as CD4+CD25high natural Tregs in a contact-independent manner. Furthermore, adoptive transfer of CD4+VEGFR1+ T cells from wild type to RAG-2-deficient C57BL/6 mice inhibited effector T-cell-mediated inflammatory bowel disease. Thus, we report CD4+ VEGFR1high T cells as a novel subset of Tregs that regulate the inflammatory response in the intestinal tract.

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Acknowledgements

This work was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &Welfare, Republic of Korea (Grant NO HI13C0954).

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Author notes

  1. Jin-Young Shin

    Present address: 5J.Y. Shin's current address is Biopharmaceutical Quality Management Division, Ministry of Food and Drug Safety, 187 Osongsaengmyeong2-ro, Osong-eup, Heungduk-gu, Cheungju-si, Chungbuk, 363-700, South Korea,

  2. Jong-Hyung Lim

    Present address: 6J.H. Lim's current address is Department of Clinical Pathobiochemistry, Faculty of Medicine, Technische Universität Dresden, Dresden 01307, Germany,

  3. Yong-Hee Kim

    Present address: 7Y.H. Kim's current address is Department of Microbiology, Kyungpook National University School of Medicine, 680 Gukchaebosang-ro, Jung-gu, Daegu 700-842, South Korea,

  4. Hyoung-Soo Cho

    Present address: 8H.S. Cho's current address is Department of Pathology, University of Massachusetts Medical School, MA 01655, USA,

  5. So-Hee Hong

    Present address: 9S.H. Hong's current address is Division of Immunology and Rheumatology, Emory University School of Medicine, GA 30322, USA,

  6. CG Park, MD, PhD, Department of Microbiology and Immunology, Department of Biomedical Sciences, Cancer Research Institute, Xenotransplantation Research Center, Seoul National University College of Medicine, 103 Daehak-ro Jongno-gu, Seoul 110-799, South Korea. E-mail: chgpark@snu.ac.kr, chgpark@gmail.com

Authors and Affiliations

  1. Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, South Korea

    Jin-Young Shin, IL-Hee Yoon, Jong-Hyung Lim, Jun-Seop Shin, Hye-Young Nam, Yong-Hee Kim, Hyoung-Soo Cho, So-Hee Hong, Jung-Sik Kim, Won-Woo Lee & Chung-Gyu Park

  2. Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea

    Jin-Young Shin, IL-Hee Yoon, Jong-Hyung Lim, Jun-Seop Shin, Hye-Young Nam, Yong-Hee Kim, Hyoung-Soo Cho, So-Hee Hong, Jung-Sik Kim & Chung-Gyu Park

  3. Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, South Korea

    Jin-Young Shin, IL-Hee Yoon, Jong-Hyung Lim, Jun-Seop Shin, Hye-Young Nam, Yong-Hee Kim, Hyoung-Soo Cho, So-Hee Hong, Jung-Sik Kim & Chung-Gyu Park

  4. Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea

    Jin-Young Shin, IL-Hee Yoon, Jong-Hyung Lim, Jun-Seop Shin, Hye-Young Nam, Yong-Hee Kim, Hyoung-Soo Cho, So-Hee Hong, Jung-Sik Kim, Won-Woo Lee & Chung-Gyu Park

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Shin, JY., Yoon, IH., Lim, JH. et al. CD4+VEGFR1HIGH T cell as a novel Treg subset regulates inflammatory bowel disease in lymphopenic mice. Cell Mol Immunol 12, 592–603 (2015). https://doi.org/10.1038/cmi.2015.71

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