title: CD4+VEGFR1(HIGH) T cell as a novel Treg subset regulates inflammatory bowel disease in lymphopenic mice.
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(+)VEGFR1(high) 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(+)VEGFR1(high) T cells are distinct from known Tregs. CD4(+)VEGFR1(high) T cells suppressed the proliferation of CD4(+)CD25(-) T cell as efficiently as CD4(+)CD25(high) 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(+) VEGFR1(high) T cells as a novel subset of Tregs that regulate the inflammatory response in the intestinal tract.
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, South Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.|Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, South Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Shin
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, South Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.|Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, South Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Il-Hee
authors.initials: IH
authors.lastname: Yoon
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, South Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.|Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, South Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Jong-Hyung
authors.initials: JH
authors.lastname: Lim
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, South Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.|Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, South Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Jun-Seop
authors.initials: JS
authors.lastname: Shin
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, South Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.|Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, South Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Nam
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, South Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.|Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, South Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Yong-Hee
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, South Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.|Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, South Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Hyoung-Soo
authors.initials: HS
authors.lastname: Cho
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, South Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.|Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, South Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: So-Hee
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, South Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.|Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, South Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Jung-Sik
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, South Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Won-Woo
authors.initials: WW
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, South Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.|Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, South Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Chung-Gyu
authors.initials: CG
authors.lastname: Park
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015704:CD4 Antigens / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000150:complications* / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008231:Lymphopenia / Q000150:complications / Q000276:immunology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009500:Neutralization Tests; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; C499308:Rag2 protein, mouse; D011948:Receptors, Antigen, T-Cell; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1