Basic Medicine, Molecular and Cellular Biology, Immunology

Microbiology and Immunology

Understanding the Key Cellular and Molecular Processes which Help the Body Control Immune-mediated Diseases

Medical Sciences Course

  • Master / Doctoral Degree


ISHII, NaotoISHII, Naoto
ISHII, Naoto

Professor, M.D. Ph.D.

Research Theme

  • Immunological memory
  • T cell-mediated autoimmune diseases
  • Inflammatory signal in T cells
Research Keywords:

autoimmunity, inflammation, T cell costimulatory signal, T cell memory, tolerance

Technical Keywords:

flowcytometry, western blot, mouse handling, cell culture, gene manipulation

Laboratory Introduction

The key function of the immune system is to attack microbes, infected cells, and tumors while ignoring the body’s own healthy cells. T cells are a subset of lymphocytes and carry out multiple functions, including activating macrophages, helping B cells produce antibody, killing infected cells, and preventing adverse immune activation. Thus, T cells play fundamental roles in controlling immunity. Our laboratory discovered two important molecules for T cells, i.e., the common γchain (γc, CD132, IL2RG) and a co-stimulatory molecule gp34 (OX40L, CD252, TNFSF4). γc serves as a shared signaling receptor for cytokines, such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, and plays essential roles for development, differentiation, and growth of T cells. gp34 is the ligand of OX40 receptor expressed on the surface of activated T cells and promotes the differentiation of antigen-primed effector and memory T cells. Although the T cell response is critical for host defense against infection and cancer, if it becomes too extensive, it can lead to immune-mediated inflammatory diseases, such as allergic asthma and rheumatoid arthritis. Since cytokine and co-stimulatory signaling pathways are attractive targets for intervention in the clinic, our laboratory seeks to understand how these pathways operate in the immune system.

Figure 1. Immunologica roles of OX40 co-stimulation

Figure 1. Immunologica roles of OX40 co-stimulation

Figure 2. Novel role of TRAF5 in controlling IL-6 signal

Figure 2. Novel role of TRAF5 in controlling IL-6 signal

Recent Publications

  • Sakurai T, Okuyama Y, Kobayashi S, et al: GITR controls intestinal inflammation by suppressing IL-15 dependent NK cell activity. *FASEB J*. in press (2020)
  • Kawabe T, Yi J, Kawajiri A, Hilligan K, et al: Requirements for the differentiation of innate T-bethigh memory-phenotype CD4+ T lymphocytes under steady state. *Nat Commun.* 11: 3366 (2020)
  • Kobayashi S、Sakurai T, So T, et al: TNF receptor-associated factor 5 limits function of plasmacytoid dendritic cells by controlling IFN regulatory factor 5 expression. *J Immunol.* 203: 1447-56 (2019)
  • Nagashima H, Okuyama Y, Fujita T: GITR co-signal in ILC2 controls allergic lung inflammation. *J Allergy Clin Immunol.* 141: 1939-1943.e8 (2018)
  • Nagashima H, Okuyama Y, Asao A, et al: TNF receptor-associated factor 5 limits inflammatory CD4+ T cell differentiation by antagonizing IL-6-receptor signaling. *Nat Immunol*, 15: 449-456 (2014)