1: A defined commensal consortium elicits CD8 T cells and anti-cancer immunity
Science of the Month - April 2019
NATURE,
565 (7741):600-+; 10.1038/s41586-019-0878-z JAN 31 2019
Takeshi Tanoue, Satoru Morita, Damian R. Plichta, Ashwin N. Skelly, Wataru Suda, Yuki Sugiura, Seiko Narushima, Hera Vlamakis, Iori Motoo, Kayoko Sugita, Atsushi Shiota, Kozue Takeshita, Keiko Yasuma-Mitobe, Dieter Riethmacher, Tsuneyasu Kaisho, Jason M. Norman, Daniel Mucida, Makoto Suematsu, Tomonori Yaguchi, Vanni Bucci, Takashi Inoue, Yutaka Kawakami, Bernat Olle, Bruce Roberts, Masahira Hattori, Ramnik J. Xavier, Koji Atarashi & Kenya Honda
Intestinal bacteria are attracting attention as a target for new therapeutic and preventive methods for various diseases. However, only a few human-derived intestinal bacterial strains that regulate the host immune system have been identified and isolated, and the relationship between CD8-positive T cells and intestinal bacteria, in particular, has remained largely unknown. We found that while the intestinal tracts of mice raised under conventional conditions have a high localization of CD8 T cells that produce interferon-gamma (IFNγ), these cells are significantly fewer in germ-free mice, which lack resident bacteria. This indicates the involvement of intestinal bacteria in the induction of these cells. Therefore, when we administered fecal samples from healthy humans to germ-free mice, we observed a strong induction of IFNγ-producing CD8 T cells with specific fecal samples. To identify the specific bacterial strains responsible, we used gnotobiotic technology (a technique to artificially control resident bacteria) to narrow down the candidates from the fecal samples, resulting in the isolation and identification of 11 intestinal bacterial strains that strongly induce IFNγ-producing CD8 T cells. When these 11 strains were administered to mice, we found that they enhanced anti-cancer immune responses and resistance to pathogenic bacteria. These results are expected to lead to the development of preventive and therapeutic methods for cancer and infectious diseases in humans.
(Kenya Honda [Class of 1973] and Takeshi Tanoue, Department of Microbiology and Immunology)
2: Megakaryocytes and platelets from a novel human adipose tissue-derived mesenchymal stem cell.
BLOOD,
133 (7):633-643; 10.1182/blood-2018-04-842641 FEB 14 2019
Keiichi Tozawa, Yukako Ono-Uruga, Masaki Yazawa, Taisuke Mori, Mitsuru Murata, Shinichiro Okamoto, Yasuo Ikeda, and Yumiko Matsubara
Platelet concentrates for transfusion have a short shelf life of four days, and their supply is 100% dependent on donors. In this paper, we report on the planned mass production of ASCL-derived platelets from an adipose tissue-derived mesenchymal stem cell line (ASCL) and their potential application in transfusion medicine. We have previously reported that mesenchymal stem cells (MSCs)/stromal cells differentiate into platelets, and as a mechanism, MSCs/stromal cells endogenously express the transcription factor NF-E2 and the cytokine thrombopoietin, which are determinants of platelet differentiation, and that stimulation by the addition of transferrin turns these factors ON, leading to platelet differentiation. In this study, we established a cell source for mass platelet production by reporting that ASCL meets the definition of MSCs set by the International Society for Cell & Gene Therapy and is more homogeneous compared to MSCs/stromal cells. We then produced ASCL-derived megakaryocytes and ASCL-derived platelets using a bioreactor, analyzed the characteristics of the resulting cells, and performed a functional comparative analysis with human peripheral blood platelets, which showed similar characteristics in aspects such as aggregation. Furthermore, they also possessed characteristics of the starting ASCL cells (surface antigens involved in cell adhesion), indicating that ASCL-derived platelets are very unique. This paper was published as a Plenary Paper in "Blood," the journal of the American Society of Hematology, and was press-released by the society.
(Yumiko Matsubara, Class of 1978, Clinical and Translational Research Center)
Other Published Papers
1: Role of cyclooxygenase-2-mediated prostaglandin E2-prostaglandin E receptor 4 signaling in cardiac reprogramming
NATURE COMMUNICATIONS,
10 10.1038/s41467-019-08626-y FEB 20 2019
Naoto Muraoka, Kaori Nara, Fumiya Tamura, Hidenori Kojima, Hiroyuki Yamakawa, Taketaro Sadahiro, Kazutaka Miyamoto, Mari Isomi, Sho Haginiwa, Hidenori Tani, Shota Kurotsu, Rina Osakabe, Satoru Torii, Shigeomi Shimizu, Hideyuki Okano, Yukihiko Sugimoto, Keiichi Fukuda & Masaki Ieda
2: Self-reactive CD4(+) IL-3(+) T cells amplify autoimmune inflammation in myocarditis by inciting monocyte chemotaxis
JOURNAL OF EXPERIMENTAL MEDICINE,
FEB 2019, 216 (2):369383;10.1084
Atsushi Anzai, John E. Mindur, Lennard Halle, Soichi Sano, Jennifer L. Choi, Shun He, Cameron S. McAlpine, Christopher T. Chan, Florian Kahles, Colin Valet, Ashley M. Fenn, Manfred Nairz, Sara Rattik, Yoshiko Iwamoto, DeLisa Fairweather, Kenneth Walsh, Peter Libby, Matthias Nahrendorf, Filip K. Swirski