FY2019 Annual Report

Immune Signal Unit

Assistant Professor Hiroki Ishikawa

Abstract

Research in our unit has focused on molecular mechanisms of differentiation of immune cells. We are particularly interested in transcriptional regulatory mechanisms of T cell differentiation. Our recent data clearly demonstrate important roles for the AP-1 transcription factor JunB in the functional diversification of T cell subsets. In this fiscal year, we investigated JunB-dependent transcriptional regulation in Treg cells.

 

1. Staff

  • Hiroki Ishikawa, Assistant Professor
  • Shin-ichi Koizumi, Postdoc
  • Daiki Sasaki, Postdoc
  • Naoyuki Taira, Postdoc
  • Mio Miyagi, Technician
  • Yu Seto, Technician
  • Tsung-Han Hsieh, Student
  • Shukla Sarker, Student
  • Ke Wang, Student
  • Tsung-Yen Huang, Student
  • Hsiao-Chiao Hsieh, Student
  • Charles Whitaker, Student
  • Mi Yang, Student
  • Rika Yoshizawa, Research Unit Administrator

 

2. Collaborations

Nothing to report.

 

3. Activities and Findings

We have recently reported that JunB regulates an IRF4-dependent eTreg transcriptional program. Like BATF and IRF4, JunB is highly expressed in CD62L–ICOS+ eTreg cells in vivo and can be induced by stimulation with anti-CD3 and anti-CD28 antibodies in the presence of IL-2 in vitro. Treg-specific JunB-deficient mice exhibit severe inflammation in the colon and lung, aberrant activation of Th1, Th2, and Th17 cells, and enhanced humoral immune responses. Unlike IRF4, JunB is not essential for eTreg generation, but JunB is required for homeostasis, colonic accumulation, and TCR-dependent suppressive functions of eTreg cells. JunB regulates expression of a subset of eTreg-related genes, such as Icos, Klrg1, T cell immunoreceptor with Ig and ITIM domains (Tigit), Ctla4, and Gzmb in Treg cells in BATF-dependent and BATF-independent manners. Mechanistically, JunB promotes DNA-binding of IRF4 at loci of eTreg-related genes containing AICE motifs, on which JunB colocalizes with BATF and IRF4, such as Icos and Ctla4.

 

4. Publications

Koizumi S and Ishikawa H, Transcriptional regulation of differentiation and functions of effector T regulatory cells. Cells, 8, 939 (2019)

 

4.3. Oral and poster presentation

Osaka U-OIST joint symposium, OIST, Jan 20, 2020 (Invited talk)

 

5. Intellectual Property Rights and Other Specific Achievements

Nothing to report.

 

6. Meetings and Events

Nothing to report.