Mammals and gut microbiota have co-evolved over 100 million years to establish a unique ecosystem based on symbiotic interactions. Colonization by gut microbiota facilitates expansion of colonic Foxp3+ regulatory T (Treg) cells, which play a pivotal role in containment of excessive inflammation. The molecular machinery controlling Treg homeostasis in the gut, however, remains largely unknown. Here we report that a DNA methylation adaptor Uhrf1 regulates homeostasis and functionality of colonic Treg cells. This mechanism secures symbiotic host-microbe interactions without an inflammatory response.
Research Area: “Epigenetic control and biological functions”
Research Theme:“Epiegenetic modifications of the gut immune system by commensal microbiota”
Yuuki Obata, Yukihiro Furusawa, Takaho A Endo, Jafar Sharif, Daisuke Takahashi, Koji Atarashi, Manabu Nakayama, Satoshi Onawa, Yumiko Fujimura, Masumi Takahashi, Tomokatsu Ikawa, Takeshi Otsubo, Yuki I Kawamura, Taeko Dohi, Shoji Tajima, Hiroshi Masumoto, Osamu Ohara, Kenya Honda, Shohei Hori, Hiroshi Ohno, Haruhiko Koseki and Koji Hase. “The epigenetic regulator Uhrf1 facilitates proliferation and maturation of colonic regulatory T cells”
Nature Immunology, Published online 28 April 2014
Koji Hase, Ph.D.
Professor, Department of Biochemistry, Faculty of Pharmacy, Keio University
Koji Matsuo, Takafumi Kawaguchi, and Yuichi Mine
Life Innovation Group, Department of Innovation Research, JST