CD4⁺ VEGFR1^HIGH T cell as a novel Treg subset regulates inflammatory bowel disease in lymphopenic mice

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.