Identifying Foxp3-expressing suppressor T cells with a bicistronic reporter.
Regulatory T cells are critical for maintaining self-tolerance and to negatively regulate immune responses. Foxp3 is a regulatory T cell-specific transcription factor that functions as the master regulator of the development and function of regulatory T cells. Here, we report the generation of a mouse model, in which a bicistronic reporter expressing a red fluorescent protein has been knocked into the endogenous Foxp3 locus. Using this mouse model, we assessed Foxp3 expression in various lymphocyte compartments and identified previously unreported Foxp3-expressing cells. In addition, we showed that de novo Foxp3 expression along with suppressive function were induced by TGF-beta in activated CD4 T cells in vitro. Finally, we demonstrated that non-Foxp3-expressing CD4 T cells could not be converted into Foxp3-expressing cells upon adoptive transfer into immunodeficient hosts. This Foxp3 bicistronic reporter knockin mouse model should greatly enhance the study of regulation and function of Foxp3-expressing regulatory T cells.
Wan
Yisong Y
YY
Section of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.
Flavell
Richard A
RA
D019264:Adoptive Transfer; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D015870:Gene Expression; D017930:Genes, Reporter; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D018448:Models, Immunological; D011994:Recombinant Proteins / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D000097573:Red Fluorescent Protein
D004247:DNA; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D008164:Luminescent Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D000097573:Red Fluorescent Protein; C498833:Foxp3 protein, mouse