Tcells that mediate autoimmune diseases such as rheumatoid arthritis (RA) are difficult to characterize because they are likely to be deleted or inactivated in the thymus if the self antigens they recognize are ubiquitously expressed. One way to obtain and analyze these autoimmune T cells is to alter T cell receptor (TCR) signaling in developing T cells to change their sensitivity to thymic negative selection, thereby allowing their thymic production. From mice thus engineered to generate Tcells mediating autoimmune arthritis, the authors isolated arthritogenic TCRs and characterized the self antigens they recognized. One of them was the ubiquitously expressed 60S ribosomal protein L23a (RPL23A), with which T cells and autoantibodies from RA patients reacted. This strategy may improve our
Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation. Morikawa H, Ohkura N, Vandenbon A, Itoh M, Nagao-Sato S, Kawaji H, Lassmann T, Carninci P, Hayashizaki Y, Forrest AR, Standley DM, Date H, Sakaguchi S; FANTOM Consortium. Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5289-94. Abstract: Naturally occurring regulatory T (Treg) cells, which specifically express the transcription factor forkhead box P3 (Foxp3), are engaged in the maintenance of immunological self-tolerance and homeostasis. By transcriptional start site cluster analysis, we assessed here how genome-wide patterns of DNA methylation or Foxp3 binding sites were associated with Treg-specific gene expression. We found that Treg-specific DNA hypomethylated reg
Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking antitumor immune responses in humans. Sugiyama D, Nishikawa H, Maeda Y, Nishioka M, Tanemura A, Katayama I, Ezoe S, Kanakura Y, Sato E, Fukumori Y, Karbach J, Jäger E, Sakaguchi S. Experimental Immunology, World Premier International Research Center, Immunology Frontier Research Center, Department of Dermatology, and Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. Proc Natl Acad Sci U S A. 2013 Oct 14. [Epub ahead of print] Abstract: CD4+ Treg cells expressing the transcription factor FOXP3 (forkhead box P3) are abundant in tumor tissues and appear to hinder the induction of effective antitumor immunity. A substantial number of T cells,
Osaka University (President: Toshio HIRANO) elected Shimon SAKAGUCHI (Deputy Dorector of IFReC) to “Distinguished Professor” of Osaka University. The new title “Distinguished Professor” was founded to honor those who have contributed to the research and management of the University. The ten professors including SAKAGUCHI assume the responsibilities of this new title on July 1, 2013.