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Kazufumi Kunimura Last modified date:2022.11.01

Assistant Professor / Division of Immunogenetics
Department of Immunobiology and Neuroscience
Medical Institute of Bioregulation

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免疫遺伝学分野 紹介HP .
Academic Degree
Ph.D., M.D.
Field of Specialization
Immunology, Cell biology
Research Interests
  • Fetomaternal immune cross-talk
    keyword : Pregnancy, Allergy
Academic Activities
1. Kazufumi Kunimura, Takehito Uruno, Yoshinori Fukui, DOCK family proteins: key players in immune surveillance mechanisms., International immunology, 10.1093/intimm/dxz067, Vol.32, No.1, pp.5-15, 2020.01, Dedicator of cytokinesis (DOCK) proteins constitute a family of evolutionarily conserved guanine nucleotide exchange factors (GEFs) for the Rho family of GTPases. Although DOCK family proteins do not contain the Dbl homology domain typically found in other GEFs, they mediate the GTP-GDP exchange reaction through the DOCK homology region-2 (DHR-2) domain. In mammals, this family consists of 11 members, each of which has unique functions depending on the expression pattern and the substrate specificity. For example, DOCK2 is a Rac activator critical for migration and activation of leukocytes, whereas DOCK8 is a Cdc42-specific GEF that regulates interstitial migration of dendritic cells. Identification of DOCK2 and DOCK8 as causative genes for severe combined immunodeficiency syndromes in humans has highlighted their roles in immune surveillance. In addition, the recent discovery of a naturally occurring DOCK2-inhibitory metabolite has uncovered an unexpected mechanism of tissue-specific immune evasion. On the other hand, GEF-independent functions have been shown for DOCK8 in antigen-induced IL-31 production in helper T cells. This review summarizes multifaced functions of DOCK family proteins in the immune system..
1. Kazufumi Kunimura, Daiji Sakata, Xin Tun, Takehito Uruno, Miho Ushijima, Tomoya Katakai, Akira Shiraishi, Ryosuke Aihara, Yasuhisa Kamikaseda, Keisuke Matsubara, Hirokazu Kanegane, Shinichiro Sawa, Gérard Eberl, Shouichi Ohga, Yasunobu Yoshikai, Yoshinori Fukui, S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer's Patches., Cell reports, 10.1016/j.celrep.2019.10.091, 29, 9, 2823-2834, 2019.11, Intestinal microfold cells (M cells) in Peyer's patches are a special subset of epithelial cells that initiate mucosal immune responses through uptake of luminal antigens. Although the cytokine receptor activator of nuclear factor-κB ligand (RANKL) expressed on mesenchymal cells triggers differentiation into M cells, other environmental cues remain unknown. Here, we show that the metastasis-promoting protein S100A4 is required for development of mature M cells. S100A4-producing cells are a heterogenous cell population including lysozyme-expressing dendritic cells and group 3 innate lymphoid cells. We found that in the absence of DOCK8, a Cdc42 activator critical for interstitial leukocyte migration, S100A4-producing cells are reduced in the subepithelial dome, resulting in a maturation defect of M cells. While S100A4 promotes differentiation into mature M cells in organoid culture, genetic inactivation of S100a4 prevents the development of mature M cells in mice. Thus, S100A4 is a key environmental cue that regulates M cell differentiation in collaboration with RANKL..
Membership in Academic Society
  • Japan Society for DOHaD (Developmental Origins of Health and Disease)
  • Japanese Society for DOHaD
  • Japanese Society of Allergology
  • Japanese Society for Immunology