Molecular Antagonism and Plasticity of Regulatory and Inflammatory T Cell Programs
Copyright policy )Molecular Antagonism and Plasticity of Regulatory and Inflammatory T Cell Programs
Regulatory T (Treg) and T helper 17 (Th17) cells were recently proposed to be reciprocally regulated during differentiation. To understand the underlying mechanisms, we utilized a Th17 reporter mouse with a red fluorescent protein (RFP) sequence inserted into the interleukin-17F (IL-17F) gene. Using IL-17F-RFP together with a Foxp3 reporter, we found that the development of Th17 and Foxp3(+) Treg cells was associated in immune responses. Although TGF-beta receptor I signaling was required for both Foxp3 and IL-17 induction, SMAD4 was only involved in Foxp3 upregulation. Foxp3 inhibited Th17 differentiation by antagonizing the function of the transcription factors RORgammat and ROR*. In contrast, IL-6 overcame this suppressive effect of Foxp3 and, together with IL-1, induced genetic reprogramming in Foxp3(+) Treg cells. STAT3 regulated Foxp3 downregulation, whereas STAT3, RORgamma, and ROR* were required for IL-17 expression in Treg cells. Our data demonstrate molecular antagonism and plasticity of Treg and Th17 cell programs.
- The University of Texas System United States
- Baylor College of Medicine (Lesotho)
- Research Triangle Park Foundation United States
- The University of Texas MD Anderson Cancer Center United States
- Baylor College of Medicine United States
Inflammation, Encephalomyelitis, Autoimmune, Experimental, Immunology, Interleukin-17, Cell Differentiation, Mice, Transgenic, T-Lymphocytes, Helper-Inducer, Flow Cytometry, Lymphocyte Activation, Polymerase Chain Reaction, T-Lymphocytes, Regulatory, Transforming Growth Factor beta1, Mice, Infectious Diseases, CELLIMMUNO, T-Lymphocyte Subsets, Transduction, Genetic, Immunology and Allergy, Animals, Immunoprecipitation, Female, MOLIMMUNO, Signal Transduction
Inflammation, Encephalomyelitis, Autoimmune, Experimental, Immunology, Interleukin-17, Cell Differentiation, Mice, Transgenic, T-Lymphocytes, Helper-Inducer, Flow Cytometry, Lymphocyte Activation, Polymerase Chain Reaction, T-Lymphocytes, Regulatory, Transforming Growth Factor beta1, Mice, Infectious Diseases, CELLIMMUNO, T-Lymphocyte Subsets, Transduction, Genetic, Immunology and Allergy, Animals, Immunoprecipitation, Female, MOLIMMUNO, Signal Transduction
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