title: Foxp3 lacking exons 2 and 7 is unable to confer suppressive ability to regulatory T cells in vivo.
abstract: The forkhead/winged-helix transcription factor FOXP3 confers suppressive ability to CD4(+)FOXP3(+) regulatory T (Treg) cells. Human Treg cells express several different isoforms of FOXP3 that differ in function. However, the regulation and functional consequences of FOXP3 isoform expression remains poorly understood. In order to study the function of the FOXP3Δ2Δ7 isoform in vivo we generated mice that exclusively expressed a Foxp3 isoform lacking exon 2 and 7. These mice exhibited multi-organ inflammation, increased cytokine production, global T cell activation, activation of antigen-presenting cells and B cell developmental defects, all features that are shared with mice completely deficient in FOXP3. Our results demonstrate that the mouse counterpart of human FOXP3Δ2Δ7 is unable to confer suppressive ability to Treg cells.
authors.affiliation: Translational Immunology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Joly
authors.affiliation: Translational Immunology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carin I M
authors.initials: CI
authors.lastname: Dahlberg
authors.affiliation: Translational Immunology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Reiner K W
authors.initials: RK
authors.lastname: Mailer
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Westerberg
authors.affiliation: Translational Immunology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. Electronic address: john.andersson@ki.se.
authors.forename: John
authors.initials: J
authors.lastname: Andersson
mesh_terms: D000818:Animals; D005091:Exons; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020033:Protein Isoforms
keywords: B cell lymphopoiesis; FOXP3; IPEX; Inflammatory disease; Isoforms; Scurfy