γδ T cells restrain extrathymic development of Foxp3+‐inducible regulatory T cells via IFN‐γ |
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Authors: | Anabelle Visperas Bo Shen Booki Min |
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Affiliation: | 1. Department of Immunology, Lerner Research Institute, Cleveland, OH, USA;2. Department of Molecular Medicine, Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA;3. Department of Gastroenterology, Cleveland Clinic Foundation, Cleveland, OH, USA |
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Abstract: | Inducible Treg (iTreg) cells generated from Ag‐stimulated naïve CD4+ T cells in the periphery play an important role in regulating immune responses. TGF‐β is a key cytokine that promotes this conversion process; however, how this process is regulated in vivo remains unclear. Here, we report that γδ T cells play a crucial role in controlling iTreg generation and suppressor function. Ag‐induced iTreg generation was significantly enhanced in C57BL/6 mice in the absence of γδ T cells. Inhibition of iTreg conversion was mediated by IFN‐γ produced by activated γδ T cells but not by activated CD4+ T cells. BM chimera experiments further confirmed γδ‐derived IFN‐γ‐dependent mechanism in regulating iTreg generation in vivo. Lastly, human peripheral blood γδ T cells also interfere with iTreg conversion via IFN‐γ. Our results suggest a novel function of γδ T cells in limiting the generation of iTreg cells, potentially balancing immunity and tolerance. |
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Keywords: | γ δ T cell CD4+ T cell IFN‐γ Inflammation Intestine iTreg cells Oral tolerance Regulatory T cells |
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